NMDA receptor - Knowledge

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with Mg) where membrane depolarization relieves the block. The discovery was thereby development of uncompetitive antagonist with longer dwell time than Mg in the channel but shorter than MK-801. That way the drug obtained would only block excessively open NMDA receptor associated channels but not normal neurotransmission. Memantine is that drug. It is a derivative of amantadine which was first an anti-influenza agent but was later discovered by coincidence to have efficacy in Parkinson's disease. Chemical structures of memantine and amantadine can be seen in figure 5. The compound was first thought to be

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conditions such as strokes and epilepsy. Treating these conditions with one of the many known NMDA receptor antagonists, however, leads to a variety of unwanted side effects, some of which can be severe. These side effects are, in part, observed because the NMDA receptors do not just signal for cell death but also play an important role in its vitality. Treatment for these conditions might be found in blocking NMDA receptors not found at the synapse. One class of excitotoxicity in disease includes gain-of-function mutations in GRIN2B and GRIN1 associated with cortical malformations, such as

1067: 535:. All the subunits share a common membrane topology that is dominated by a large extracellular N-terminus, a membrane region comprising three transmembrane segments, a re-entrant pore loop, an extracellular loop between the transmembrane segments that are structurally not well known, and an intracellular C-terminus, which are different in size depending on the subunit and provide multiple sites of interaction with many intracellular proteins. Figure 1 shows a basic structure of GluN1/GluN2 subunits that forms the 418: 1082: 504: 11923: 181:

through the open ion channel. A voltage-dependent flow of predominantly calcium (Ca), sodium (Na), and potassium (K) ions into and out of the cell is made possible by the depolarization of the cell, which displaces and repels the Mg and Zn ions from the pore. Ca flux through NMDA receptors in particular is thought to be critical in synaptic plasticity, a cellular mechanism for learning and memory, due to proteins which bind to and are activated by Ca ions.

381:. Extrasynaptic NMDA receptors promote death signaling; they cause transcriptional shut-off, mitochondrial dysfunction, and structural disintegration. This pathological triad of extrasynaptic NMDA receptor signaling represents a common conversion point in the etiology of several acute and chronic neurodegenerative conditions. The molecular basis for toxic extrasynaptic NMDA receptor signaling was uncovered by Hilmar Bading and co-workers in 2020. 807:. More importantly, each GluN2 subunit has a different intracellular C-terminal domain that can interact with different sets of signaling molecules. Unlike GluN1 subunits, GluN2 subunits are expressed differentially across various cell types and developmental timepoints and control the electrophysiological properties of the NMDA receptor. In classic circuits, GluN2B is mainly present in immature neurons and in extrasynaptic locations such as 2292: 34: 547: 721:

Memantine only blocks NMDA receptor associated channels during prolonged activation of the receptor, as it occurs under excitotoxic conditions, by replacing magnesium at the binding site. During normal receptor activity the channels only stay open for several milliseconds and under those circumstances memantine is unable to bind within the channels and therefore does not interfere with normal synaptic activity.

11935: 8763: 1370: 1567: 1405: 2233:, and partially inhibited by the ambient concentration of H under physiological conditions. The level of inhibition by H is greatly reduced in receptors containing the NR1a subtype, which contains the positively charged insert Exon 5. The effect of this insert may be mimicked by positively charged polyamines and aminoglycosides, explaining their mode of action. 2530:). Magnesium works to potentiate NMDA-induced responses at positive membrane potentials while blocking the NMDA channel. The use of calcium, potassium, and sodium are used to modulate the activity of NMDARs passing through the NMDA membrane. Changes in H concentration can partially inhibit the activity of NMDA receptors in different physiological conditions. 2452:. Blocking of NMDA receptors could therefore, in theory, be useful in treating such diseases. It is, however, important to preserve physiological NMDA receptor activity while trying to block its excessive, excitotoxic activity. This can possibly be achieved by uncompetitive antagonists, blocking the receptor's ion channel when excessively open 2403:

open NMDA receptor channels and making it a much better neuroprotective drug than amantadine. The binding pockets for the methyl groups are considered to be at the NR1-A645 and NR2B-A644 of the NR1/NR2B. The binding pockets are shown in figure 2. Memantine binds at or near to the Mg site inside the NMDA receptor associated channel. The -NH

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specific NMDARs. In addition, the theory of subunit variation does not explain how this effect might predominate, as it is widely held that the most common tetramer, made from two GluN1 subunits and one of each subunit GluN2A and GluN2B, makes up a high percentage of the NMDARs. The subunit composition of

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makeup. NMDA receptors are heterotetramers with two GluN1 subunits and two variable subunits. Two of these variable subunits, GluN2A and GluN2B, have been shown to preferentially lead to cell survival and cell death cascades respectively. Although both subunits are found in synaptic and extrasynaptic

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is an example of an uncompetitive channel blocker of the NMDA receptor, with a relatively rapid off-rate and low affinity. At physiological pH its amine group is positively charged and its receptor antagonism is voltage-dependent. It thereby mimics the physiological function of Mg as channel blocker.

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GluN1/GluN2B transmembrane segments are considered to be the part of the receptor that forms the binding pockets for uncompetitive NMDA receptor antagonists, but the transmembrane segments structures are not fully known as stated above. It is claimed that three binding sites within the receptor, A644

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is a second-generation derivative of memantine, it reduces excitotoxicity mediated by overactivation of the glutamatergic system by blocking NMDA receptor without sacrificing safety. Provisional studies in animal models show that nitromemantines are more effective than memantine as neuroprotectants,

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that usually induces LTP with synaptic NMDARs, when applied selectively to extrasynaptic NMDARs produces a LTD. Experimentation also indicates that extrasynaptic activity is not required for the formation of LTP. In addition, both synaptic and extrasynaptic activity are involved in expressing a full

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and aminoadamantane can be used as a target-directed shuttle to bring nitrogen oxide (NO) close to the site within the NMDA receptor where it can nitrosylate and regulate the ion channel conductivity. A NO donor that can be used to decrease NMDA receptor activity is the alkyl nitrate nitroglycerin.

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NMDARs there is some evidence to suggest that the GluN2B subunit occurs more frequently in extrasynaptic receptors. This observation could help explain the dualistic role that NMDA receptors play in excitotoxicity. t-NMDA receptors have been implicated in excitotoxicity-mediated death of neurons in

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NMDA receptors (NMDARs) critically influence the induction of synaptic plasticity. NMDARs trigger both long-term potentiation (LTP) and long-term depression (LTD) via fast synaptic transmission. Experimental data suggest that extrasynaptic NMDA receptors inhibit LTP while producing LTD. Inhibition

970:). Extrasynaptic stimulation NMDARs regulated p38MAPK in the opposite fashion, causing an increase in intracellular concentration. Experiments of this type have since been repeated with the results indicating these differences stretch across many pathways linked to cell survival and excitotoxicity. 876:

subunits become more numerous than GluN2B. This is called the GluN2B-GluN2A developmental switch, and is notable because of the different kinetics each GluN2 subunit contributes to receptor function. For instance, greater ratios of the GluN2B subunit leads to NMDA receptors which remain open longer

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Overactivation of NMDA receptors, causing excessive influx of Ca can lead to excitotoxicity. Excitotoxicity is implied to be involved in some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and Huntington's disease. Blocking of NMDA receptors could therefore, in theory,

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near 0 mV. While the opening and closing of the ion channel is primarily gated by ligand binding, the current flow through the ion channel is voltage-dependent. Specifically located on the receptor, extracellular magnesium (Mg) and zinc (Zn) ions can bind and prevent other cations from flowing

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of the postsynaptic membrane, which relieves the voltage-dependent channel block by Mg. Activation and opening of the receptor channel thus allows the flow of K, Na and Ca ions, and the influx of Ca triggers intracellular signaling pathways. Allosteric receptor binding sites for zinc, proteins and

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of (71.0+11.1) μM. The binding site with the highest affinity is called the dominant binding site. It involves a connection between the amine group of memantine and the NR1-N161 binding pocket of the NR1/NR2B subunit. The methyl side groups play an important role in increasing the affinity to the

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Because of these adverse side effects of high affinity blockers, the search for clinically successful NMDA receptor antagonists for neurodegenerative diseases continued and focused on developing low affinity blockers. However the affinity could not be too low and dwell time not too short (as seen

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appear to contribute to cell death, there is evidence to suggest that stimulation of synaptic NMDA receptors contributes to the health and longevity of the cell. There is ample evidence to support the dual nature of NMDA receptors based on location, and the hypothesis explaining the two differing

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via three distinct subunits, namely GluN1, GluN2, and GluN3. The GluN1 subunit, which is encoded by the GRIN1 gene, exhibits eight distinct isoforms owing to alternative splicing. On the other hand, the GluN2 subunit, of which there are four different types (A-D), as well as the GluN3 subunit, of

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NMDA receptor function is also strongly regulated by chemical reduction and oxidation, via the so-called "redox modulatory site." Through this site, reductants dramatically enhance NMDA channel activity, whereas oxidants either reverse the effects of reductants or depress native responses. It is

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are activated by NMDA receptors based on its location within the cell membrane. Experiments have been designed to stimulate either synaptic or non-synaptic NMDA receptors exclusively. These types of experiments have shown that different pathways are being activated or regulated depending on the

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Granule cell precursors (GCPs) of the cerebellum, after undergoing symmetric cell division in the external granule-cell layer (EGL), migrate into the internal granule-cell layer (IGL) where they down-regulate GluN2B and activate GluN2C, a process that is independent of neuregulin beta signaling

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NMDA receptor antagonists, which were developed first, are not a good option because they compete and bind to the same site (NR2 subunit) on the receptor as the agonist, glutamate, and therefore block normal function also. They will block healthy areas of the brain prior to having an impact on

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Despite the compelling evidence and the relative simplicity of these two theories working in tandem, there is still disagreement about the significance of these claims. Some problems in proving these theories arise with the difficulty of using pharmacological means to determine the subtypes of

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Uncompetitive NMDA receptor antagonists block within the ion channel at the Mg site (pore region) and prevent excessive influx of Ca. Noncompetitive antagonism refers to a type of block that an increased concentration of glutamate cannot overcome, and is dependent upon prior activation of the

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The GluN2B subunit has been involved in modulating activity such as learning, memory, processing and feeding behaviors, as well as being implicated in number of human derangements. The basic structure and functions associated with the NMDA receptor can be attributed to the GluN2B subunit. For

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Memantine (1-amino-3,5-dimethyladamantane) is an aminoalkyl cyclohexane derivative and an atypical drug compound with non-planar, three dimensional tricyclic structure. Figure 8 shows SAR for aminoalkyl cyclohexane derivative. Memantine has several important features in its structure for its

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conditions since the late 1950s. NMDA receptors seem to play an important role in many of these degenerative diseases affecting the brain. Most notably, excitotoxic events involving NMDA receptors have been linked to Alzheimer's disease and Huntington's disease, as well as with other medical

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Martynyuk AE, Seubert CN, Yarotskyy V, Glushakov AV, Gravenstein N, Sumners C, Dennis DM (November 2006). "Halogenated derivatives of aromatic amino acids exhibit balanced antiglutamatergic actions: potential applications for the treatment of neurological and neuropsychiatric disorders".

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be useful in treating such diseases. It is, however, important to preserve physiological NMDA receptor activity while trying to block its excessive, excitotoxic activity. This can possibly be achieved by uncompetitive antagonists, blocking the receptors ion channel when excessively open.

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are examples of such antagonists, see figure 1. The off-rate of an antagonist from the receptors channel is an important factor as too slow off-rate can interfere with normal function of the receptor and too fast off-rate may give ineffective blockade of an excessively open receptor.

2476:. However, the NMDA receptor cation channel is blocked by Mg at resting membrane potential. Magnesium unblock is not instantaneous; to unblock all available channels, the postsynaptic cell must be depolarized for a sufficiently long period of time (in the scale of milliseconds). 1617:), as well as some NMDA receptor antagonists used only in research environments. So far, the published research on Olney's lesions is inconclusive in its occurrence upon human or monkey brain tissues with respect to an increase in the presence of NMDA receptor antagonists. 2338:, which for example anticholinergic drugs do not do much good for. It helps recovery of synaptic function and in that way improves impaired memory and learning. In 2015 memantine is also in trials for therapeutic importance in additional neurological disorders. 6239:

Chen PE, Geballe MT, Stansfeld PJ, Johnston AR, Yuan H, Jacob AL, et al. (May 2005). "Structural features of the glutamate binding site in recombinant NR1/NR2A N-methyl-D-aspartate receptors determined by site-directed mutagenesis and molecular modeling".

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and colleagues. In the early 1980s, NMDA receptors were shown to be involved in several central synaptic pathways. Receptor subunit selectivity was discovered in the early 1990s, which led to recognition of a new class of compounds that selectively inhibit the

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Many second-generation memantine derivatives have been in development that may show even better neuroprotective effects, where the main thought is to use other safe but effective modulatory sites on the NMDA receptor in addition to its associated ion channel.

8648: 2483:". Its ion channel opens only when the following two conditions are met: glutamate is bound to the receptor, and the postsynaptic cell is depolarized (which removes the Mg blocking the channel). This property of the NMDA receptor explains many aspects of 2716:. Experiments in which rodents are treated with NMDA receptor antagonist are today the most common model when it comes to testing of novel schizophrenia therapies or exploring the exact mechanism of drugs already approved for treatment of schizophrenia. 1388:, with memantine as the template, as NMDA receptor antagonists. Neramexane binds to the same site as memantine within the NMDA receptor associated channel and with comparable affinity. It does also show very similar bioavailability and blocking kinetics 2436:(X= 1 or 2) group for interaction with the S- nitrosylation/redox site external to the memantine binding site. Lengthening the side chains of memantine compensates for the worse drug affinity in the channel associated with the addition of the –ONO 437:-) NMDARs (e.g., GluN1-2A-1-2A). Triheteromeric NMDARs, by contrast, contain three different types of subunits (e.g., GluN1-2A-1-2B), and include receptors that are composed of one or more subunits from each of the three gene families, designated 2258:

The main problem with the development of NMDA antagonists for neuroprotection is that physiological NMDA receptor activity is essential for normal neuronal function. Complete blockade of all NMDA receptor activity results in side effects such as

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group on memantine, which is protonated under physiological pH of the body, represents the region that binds at or near to the Mg site. Adding two methyl groups to the -N on the memantine structure has shown to decrease affinity, giving an

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Memantine is an example of uncompetitive NMDA receptor antagonist that has approved indication for the neurodegenerative disease Alzheimer's disease. In 2015 memantine is still in clinical trials for additional neurological diseases.

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The glycine-binding modules of the GluN1 and GluN3 subunits and the glutamate-binding module of the GluN2A subunit have been expressed as soluble proteins, and their three-dimensional structure has been solved at atomic resolution by

409:. It was not until 1972 that a possible therapeutic importance of memantine for treating neurodegenerative disorders was discovered. From 1989 memantine has been recognized to be an uncompetitive antagonist of the NMDA receptor. 376:

and co-workers that the cellular consequences of NMDA receptor stimulation depend on the receptor's location on the neuronal cell surface. Synaptic NMDA receptors promote gene expression, plasticity-related events, and acquired

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of adamantane derivatives in the context of diseases affecting the CNS. Before this finding, memantine, another adamantane derivative, had been synthesized by Eli Lilly and Company in 1963. The purpose was to develop a

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which there are two types (A and B), are each encoded by six separate genes. This intricate molecular structure and genetic diversity enable the receptor to carry out a wide range of physiological functions within the

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is that the physiological actions of the NMDA receptor are essential for normal neuronal function. To be clinically useful NMDA antagonists need to block excessive activation without interfering with normal functions.

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Georgiev D, Taniura H, Kambe Y, Takarada T, Yoneda Y (August 2008). "A critical importance of polyamine site in NMDA receptors for neurite outgrowth and fasciculation at early stages of P19 neuronal differentiation".

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Gibson DA, Harris BR, Rogers DT, Littleton JM (October 2002). "Radioligand binding studies reveal agmatine is a more selective antagonist for a polyamine-site on the NMDA receptor than arcaine or ifenprodil".

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which is implied to be involved in some neurodegenerative disorders. Blocking of NMDA receptors could therefore, in theory, be useful in treating such diseases. However, hypofunction of NMDA receptors (due to

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neuronal death. The developmental switch in subunit composition is thought to explain the developmental changes in NMDA neurotoxicity. Homozygous disruption of the gene for GluN2B in mice causes perinatal

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ions which are only removed when the neuron is sufficiently depolarized. Thus, the channel acts as a "coincidence detector" and only once both of these conditions are met, the channel opens and it allows

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Skolnick P, Boje K, Miller R, Pennington M, Maccecchini ML (October 1992). "Noncompetitive inhibition of N-methyl-D-aspartate by conantokin-G: evidence for an allosteric interaction at polyamine sites".

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Mueller AL, Artman LD, Balandrin MF, Brady E, Chien Y, DelMar EG, et al. (2000). "NPS 1506, a moderate affinity uncompetitive NMDA receptor antagonist: preclinical summary and clinical experience".

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compared to those with more GluN2A. This may in part account for greater memory abilities in the immediate postnatal period compared to late in life, which is the principle behind genetically altered '

966:, but are regulated oppositely by NMDARs depending on its location. For example, synaptic NMDA excitation caused a decrease in the intracellular concentration of p38 mitogen-activated protein kinase ( 10141: 9847: 8643:

Todd A Hardy, Reddel, Barnett, Palace, Lucchinetti, Weinshenker, Atypical inflammatory demyelinating syndromes of the CNS, The lancet neurology, Volume 15, Issue 9, August 2016, Pages 967-981, doi:

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Despite the small structural difference between memantine and amantadine, two adamantane derivatives, the affinity for the binding site of NR1/NR2B subunit is much greater for memantine. In

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Yarotskyy V, Glushakov AV, Sumners C, Gravenstein N, Dennis DM, Seubert CN, Martynyuk AE (May 2005). "Differential modulation of glutamatergic transmission by 3,5-dibromo-L-phenylalanine".

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Since two molecules of glutamate and glycine each are thought to be required for channel activation (3, 6), this implies that the NMDA receptor should be composed of at least four subunits.

2044:-, which is a safe donor that avoids neurotoxicity. The nitro group must be targeted to the NMDA receptor, otherwise other effects of NO such as dilatation of blood vessels and consequent 8335: 10395: 592:

between two GluN1 and two GluN2 subunits (the subunits were previously denoted as GluN1 and GluN2), two obligatory GluN1 subunits and two regionally localized GluN2 subunits. A related

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Steullet P, Neijt HC, Cuénod M, Do KQ (February 2006). "Synaptic plasticity impairment and hypofunction of NMDA receptors induced by glutathione deficit: relevance to schizophrenia".

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Nadler V, Mechoulam R, Sokolovsky M (September 1993). "Blockade of 45Ca2+ influx through the N-methyl-D-aspartate receptor ion channel by the non-psychoactive cannabinoid HU-211".

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Danysz W, Parsons CG (September 2003). "The NMDA receptor antagonist memantine as a symptomatological and neuroprotective treatment for Alzheimer's disease: preclinical evidence".

3750:"Failures and successes of NMDA receptor antagonists: molecular basis for the use of open-channel blockers like memantine in the treatment of acute and chronic neurologic insults" 9596: 2690:(also known as NMDAR encephalitis), that usually occurs due to cross-reactivity of antibodies produced by the immune system against ectopic brain tissues, such as those found in 12207: 12202: 12132: 2197:

generally block NMDA current activity in a noncompetitive and a voltage-independent manner. However zinc may potentiate or inhibit the current depending on the neural activity.

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activation, it is seen to reduce methamphetamine induced brain damage through CB1-dependent and independent mechanisms, respectively, and inhibition of methamphetamine induced

12217: 9630: 1128:-serine can be released both by neurons and astrocytes to regulate NMDA receptors. Note that D-serine has also been shown to work as an antagonist / inverse co-agonist for 12137: 557:

Mg blocks the NMDA receptor channel in a voltage-dependent manner. The channels are also highly permeable to Ca. Activation of the receptor depends on glutamate binding,

12222: 12167: 10366: 2383:) side groups which serve to prolong the dwell time and increase stability as well as affinity for the NMDA receptor channel compared with amantadine (1-adamantanamine). 425:

Functional NMDA receptors are heterotetramers comprising different combinations of the GluN1, GluN2 (A-D), and GluN3 (A-B) subunits derived from distinct gene families (

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Koch HJ, Szecsey A, Haen E (1 January 2004). "NMDA-antagonism (memantine): an alternative pharmacological therapeutic principle in Alzheimer's and vascular dementia".

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Vyklicky, V.; Korinek, M.; Smejkalova, T.; Balik, A.; Krausova, B.; Kaniakova, M.; Lichnerova, K.; Cerny, J.; Krusek, J.; Dittert, I.; Horak, M.; Vyklicky, L. (2014).

881:'. The detailed time course of this switch in the human cerebellum has been estimated using expression microarray and RNA seq and is shown in the figure on the right. 311:

deficiency or other causes) may be involved in impairment of synaptic plasticity and could have other negative repercussions. The main problem with the utilization of

2267:. To be clinically relevant, an NMDA receptor antagonist must limit its action to blockade of excessive activation, without limiting normal function of the receptor. 936:, there has been much discussion on how these receptors can affect both cell survival and cell death. Recent evidence supports the hypothesis that overstimulation of 10512: 697:

Uncompetitive NMDA receptor antagonists, or channel blockers, enter the channel of the NMDA receptor after it has been activated and thereby block the flow of ions.

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Loftis JM, Janowsky A (January 2003). "The N-methyl-D-aspartate receptor subunit NR2B: localization, functional properties, regulation, and clinical implications".

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with distinct brain distributions and functional properties arise by selective splicing of the GluN1 transcripts and differential expression of the GluN2 subunits.

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Motor Discoordination Results from Combined Gene Disruption of the NMDA Receptor NR2A and NR2C Subunits, But Not from Single Disruption of the NR2A or NR2C Subunit

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Yan J, Bengtson CP, Buchthal B, Hagenston AM, Bading H (October 2020). "Coupling of NMDA receptors and TRPM4 guides discovery of unconventional neuroprotectants".

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subunit. These findings led to vigorous campaign in the pharmaceutical industry. From this it was considered that NMDA receptors were associated with a variety of

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than pathological areas. These antagonists can be displaced from the receptor by high concentration of glutamate which can exist under excitotoxic circumstances.

12097: 2498:, the NMDA receptor pore is opened allowing for an influx of external magnesium ions binding to prevent further ion permeation. External magnesium ions are in a 2203:

is a potent NMDAR antagonist. Presynaptic deficits resulting from Pb exposure during synaptogenesis are mediated by disruption of NMDAR-dependent BDNF signaling.

12043: 10327: 12212: 11593: 9569: 7054:"Specific inhibition of N-methyl-D-aspartate receptor function in rat hippocampal neurons by L-phenylalanine at concentrations observed during phenylketonuria" 8486: 441:-NMDARs (e.g., GluN1-2A-3A-2A). There is one GluN1, four GluN2, and two GluN3 subunit encoding genes, and each gene may produce more than one splice variant. 12147: 433:). All NMDARs contain two of the obligatory GluN1 subunits, which when assembled with GluN2 subunits of the same type, give rise to canonical diheteromeric ( 666:. This has revealed a common fold with amino acid-binding bacterial proteins and with the glutamate-binding module of AMPA-receptors and kainate-receptors. 12122: 10024: 2210:

class I are endogenous negative regulators of NMDAR-mediated currents in the adult hippocampus, and are required for appropriate NMDAR-induced changes in

12172: 11586: 8816: 5676:"Soluble Aβ oligomers inhibit long-term potentiation through a mechanism involving excessive activation of extrasynaptic NR2B-containing NMDA receptors" 2448:

Excitotoxicity is implied to be involved in some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease and

7671:"Lead exposure during synaptogenesis alters vesicular proteins and impairs vesicular release: potential role of NMDA receptor-dependent BDNF signaling" 8320: 12127: 12102: 9562: 8227:

Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A (February 1984). "Magnesium gates glutamate-activated channels in mouse central neurones".

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Moriyoshi K, Masu M, Ishii T, Shigemoto R, Mizuno N, Nakanishi S (November 1991). "Molecular cloning and characterization of the rat NMDA receptor".

2712:, the NMDAR antagonist phencyclidine can produce a wider range of symptoms that resemble schizophrenia in healthy volunteers, in what has led to the 2672: 4318: 2657:. In animal models, tianeptine inhibits the pathological stress-induced changes in glutamatergic neurotransmission in the amygdala and hippocampus. 12092: 10909: 10034: 8914: 7577:"Na/Ca exchanger isoform 1 takes part to the Ca-related prosurvival pathway of SOD1 in primary motor neurons exposed to beta-methylamino-L-alanine" 3894:

Hardingham GE, Fukunaga Y, Bading H (May 2002). "Extrasynaptic NMDARs oppose synaptic NMDARs by triggering CREB shut-off and cell death pathways".

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Sonkusare SK, Kaul CL, Ramarao P (January 2005). "Dementia of Alzheimer's disease and other neurodegenerative disorders--memantine, a new hope".

1473:(NRX-1074) are now viewed for the development of new drugs with antidepressant and analgesic effects without obvious psychotomimetic activities. 396:

as flu medicine and experienced remarkable remission of her Parkinson's symptoms. This finding, reported by Scawab et al., was the beginning of

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are also partially due to their effects at blocking NMDA receptor activity. In contrast, overactivation of NMDAR by NMDA agonists increases the

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McEwen BS, Chattarji S (December 2004). "Molecular mechanisms of neuroplasticity and pharmacological implications: the example of tianeptine".

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on the GluNB subunit and A645 and N616 on the GluN1 subunit, are important for binding of memantine and related compounds as seen in figure 2.

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unbinding kinetics, increasing channel open probability with depolarization. This property is fundamental to the role of the NMDA receptor in

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and glutamate bind to it. The receptor is a highly complex and dynamic heteromeric protein that interacts with a multitude of intracellular

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links to a membrane domain, which consists of three transmembrane segments and a re-entrant loop reminiscent of the selectivity filter of

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example, the glutamate binding site and the control of the Mg block are formed by the GluN2B subunit. The high affinity sites for glycine

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Several derivatives of Nitromemantine, a second-generation derivative of memantine, have been synthesized in order to perform a detailed

2792:"Molecular determinants of agonist discrimination by NMDA receptor subunits: analysis of the glutamate binding site on the NR2B subunit" 12058: 10775: 10760: 10532: 10527: 10415: 7626:

Horning MS, Trombley PQ (October 2001). "Zinc and copper influence excitability of rat olfactory bulb neurons by multiple mechanisms".

1903: 11295: 11290: 11285: 11280: 10812: 10232: 9707: 7839:"MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term depression" 2768: 1450:-phenylalanine has been proposed a novel therapeutic drug candidate for treatment of neuropsychiatric disorders and diseases such as 907:, whereas disruption of the GluN2A gene produces viable mice, although with impaired hippocampal plasticity. One study suggests that 37:

Stylized depiction of an activated NMDAR. Glutamate is in the glutamate-binding site and glycine is in the glycine-binding site. The

6143:"Early increase in extrasynaptic NMDA receptor signaling and expression contributes to phenotype onset in Huntington's disease mice" 2464:

The NMDA receptor is a non-specific cation channel that can allow the passage of Ca and Na into the cell and K out of the cell. The

4769:"Analysis of synaptic gene expression in the neocortex of primates reveals evolutionary changes in glutamatergic neurotransmission" 1917: 8778: 7532:

Yu XM, Askalan R, Keil GJ, Salter MW (January 1997). "NMDA channel regulation by channel-associated protein tyrosine kinase Src".

2468:(EPSP) produced by activation of an NMDA receptor increases the concentration of Ca in the cell. The Ca can in turn function as a 678:

rely on the mechanism of NMDA receptors. NMDA receptors are glutamate-gated cation channels that allow for an increase of calcium

12272: 12117: 12112: 11627: 9902: 8809: 3272:"Cannabinoid receptors couple to NMDA receptors to reduce the production of NO and the mobilization of zinc induced by glutamate" 2839:"Identification of amino acid residues of the NR2A subunit that control glutamate potency in recombinant NR1/NR2A NMDA receptors" 153:, meaning it is a protein which allows the passage of ions through the cell membrane. The NMDA receptor is so named because the 10795: 10630: 10044: 9877: 9812: 6817:"Neuroactive compounds obtained from arthropod venoms as new therapeutic platforms for the treatment of neurological disorders" 1628:

of the channel pore or are antagonists of the glycine co-regulatory site rather than antagonists of the active/glutamate site.

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NMDA receptor (NMDAR)-mediated currents are directly related to membrane depolarization. NMDA agonists therefore exhibit fast

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of the NMDA receptor, entering the channel of the receptor after it has been activated and thereby blocking the flow of ions.

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Liu DD, Yang Q, Li ST (April 2013). "Activation of extrasynaptic NMDA receptors induces LTD in rat hippocampal CA1 neurons".

5378:. New York, NY, USA: Weill Medical College of Cornell University, Department of Neurology and Neuroscience. pp. 553–569. 4333: 2713: 2480: 967: 41:, which modulates receptor function when bound to a ligand, is not occupied. NMDARs require the binding of two molecules of 12177: 872:

is predominant in the early postnatal brain, the number of GluN2A subunits increases during early development; eventually,

674:

NMDA receptors are a crucial part of the development of the central nervous system. The processes of learning, memory, and

6516:"Positive N-Methyl-D-Aspartate Receptor Modulation by Rapastinel Promotes Rapid and Sustained Antidepressant-Like Effects" 4575:"Effect of the N-methyl-D-aspartate NR2B subunit antagonist ifenprodil on precursor cell proliferation in the hippocampus" 977:, and Jacob. ERK1/2 is responsible for phosphorylation of Jacob when excited by synaptic NMDARs. This information is then 860: 799:). Strong evidence shows that the genes encoding the GluN2 subunits in vertebrates have undergone at least two rounds of 12282: 11672: 11514: 10341: 8802: 8149:"Fast and slow voltage-dependent dynamics of magnesium block in the NMDA receptor: the asymmetric trapping block model" 6498: 2695: 2671:

for the treatment of moderate-to-severe Alzheimer's disease, and has now received a limited recommendation by the UK's

2057:

and in vivo. Memantine and newer derivatives could become very important weapons in the fight against neuronal damage.

764: 9225: 9213: 8487:"Tianeptine: a novel atypical antidepressant that may provide new insights into the biomolecular basis of depression" 7886:

Traynelis SF, Cull-Candy SG (May 1990). "Proton inhibition of N-methyl-D-aspartate receptors in cerebellar neurons".

7143:-Methyl-D-Aspartate (NMDA)-Receptor Antagonism on Hyperalgesia, Opioid Use, and Pain After Radical Prostatectomy" at 2641: 2465: 1913: 999: 8197: 8117: 7937:

Aizenman E, Lipton SA, Loring RH (March 1989). "Selective modulation of NMDA responses by reduction and oxidation".

6643:

Vécsei L, Szalárdy L, Fülöp F, Toldi J (January 2013). "Kynurenines in the CNS: recent advances and new questions".

5018:"Developmental changes in NMDA neurotoxicity reflect developmental changes in subunit composition of NMDA receptors" 4877:"Switching of NMDA receptor 2A and 2B subunits at thalamic and cortical synapses during early postnatal development" 2298:

The chemical structures of MK-801, phencyclidine and ketamine, high affinity uncompetitive NMDA receptor antagonists

9245: 9122: 2432:), showed a promising outcome. Nitromemantine utilizes memantine binding site on the NMDA receptor to target the NO 2207: 1482: 1432:(NMDA), which the NMDA receptor was named after, is a partial agonist of the active or glutamate recognition site. 620:-binding domain. GluN1 subunits bind the co-agonist glycine and GluN2 subunits bind the neurotransmitter glutamate. 7149: 4969:"NMDA receptor subunits have differential roles in mediating excitotoxic neuronal death both in vitro and in vivo" 2970:

Furukawa H, Singh SK, Mancusso R, Gouaux E (November 2005). "Subunit arrangement and function in NMDA receptors".

12277: 6106:

Lucas DR, Newhouse JP (August 1957). "The toxic effect of sodium L-glutamate on the inner layers of the retina".

5165:"Timing neurogenesis and differentiation: insights from quantitative clonal analyses of cerebellar granule cells" 2687: 2421: 973:

Two specific proteins have been identified as a major pathway responsible for these different cellular responses

8794: 8710:"Lasting s-ketamine block of spreading depolarizations in subarachnoid hemorrhage: a retrospective cohort study" 3993:"Therapeutic targeting of the pathological triad of extrasynaptic NMDA receptor signaling in neurodegenerations" 3607:

Lipton SA (February 2006). "Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond".

389:(also known as interface inhibitors) disrupt the NMDAR/TRPM4 complex and detoxify extrasynaptic NMDA receptors. 11939: 11871: 10499: 9258: 8633:

Azheimer's disease - donepezil, galantamine, rivastigmine and memantine (review): final appraisal determination

8354:"The neurobiological properties of tianeptine (Stablon): from monoamine hypothesis to glutamatergic modulation" 4720:"Hierarchy of transcriptomic specialization across human cortex captured by structural neuroimaging topography" 3182:

Cull-Candy S, Brickley S, Farrant M (June 2001). "NMDA receptor subunits: diversity, development and disease".

3125: 2626: 2145:

do not directly activate NMDA receptors, but instead act to potentiate or inhibit glutamate-mediated responses.

1971: 1326: 823: 121:). However, the binding of the ligands is typically not sufficient to open the channel as it may be blocked by 7350:

Huggins DJ, Grant GH (January 2005). "The function of the amino terminal domain in NMDA receptor modulation".

3797:

Yamakura T, Shimoji K (October 1999). "Subunit- and site-specific pharmacology of the NMDA receptor channel".

1116:

has also been found to co-agonize the NMDA receptor with even greater potency than glycine. It is produced by

1100:(aspartate does not stimulate the receptors as strongly). In addition, NMDARs also require the binding of the 10247: 9585: 8531: 4226:

Kristiansen LV, Huerta I, Beneyto M, Meador-Woodruff JH (February 2007). "NMDA receptors and schizophrenia".

2756: 2449: 2075: 1303: 1124:-serine can block NMDA-mediated excitatory neurotransmission in many areas. Recently, it has been shown that 679: 91: 8708:

Santos E, Olivares-Rivera A, Major S, Sánchez-Porras R, Uhlmann L, Kunzmann K, et al. (December 2019).

5537:"Extrasynaptic NMDA receptors couple preferentially to excitotoxicity via calpain-mediated cleavage of STEP" 5439:"Memantine preferentially blocks extrasynaptic over synaptic NMDA receptor currents in hippocampal autapses" 4622:"NMDA receptors subserve persistent neuronal firing during working memory in dorsolateral prefrontal cortex" 11579: 8446:"Neurobiology of mood, anxiety, and emotions as revealed by studies of a unique antidepressant: tianeptine" 6451:"Efficacy of 3,5-dibromo-L-phenylalanine in rat models of stroke, seizures and sensorimotor gating deficit" 6331:"The t-N-methyl-d-aspartate receptor: Making the case for d-Serine to be considered its inverse co-agonist" 4146:"The t-N-methyl-d-aspartate receptor: Making the case for d-Serine to be considered its inverse co-agonist" 2637: 382: 107: 1049:-NMDA receptors, which is made in the brain, has been shown to mitigate neuron loss in an animal model of 834:. This is consistent with the expansion in GluN2B actions and expression across the cortical hierarchy in 12021: 11620: 10874: 5214:"Neuregulin signaling is dispensable for NMDA- and GABA(A)-receptor expression in the cerebellum in vivo" 945: 937: 657:, as well as residues that interact with a large number of structural, adaptor, and scaffolding proteins. 280: 244: 8661:"Circuit-based framework for understanding neurotransmitter and risk gene interactions in schizophrenia" 8632: 603:

Each receptor subunit has modular design and each structural module, also represents a functional unit:

11876: 11861: 10667: 9280: 9237: 7575:

Petrozziello T, Boscia F, Tedeschi V, Pannaccione A, de Rosa V, Corvino A, et al. (January 2022).

7436:"Cdk5 regulates the phosphorylation of tyrosine 1472 NR2B and the surface expression of NMDA receptors" 6016:"The anchoring protein SAP97 influences the trafficking and localisation of multiple membrane channels" 5586:"Encoding and transducing the synaptic or extrasynaptic origin of NMDA receptor signals to the nucleus" 2495: 1891:

Some common agents in which weak NMDA receptor antagonism is a secondary or additional action include:

1593:. When certain NMDA receptor antagonists are given to rodents in large doses, they can cause a form of 7093:

Glushakov AV, Glushakova O, Varshney M, Bajpai LK, Sumners C, Laipis PJ, et al. (February 2005).

6901:

Feigenbaum JJ, Bergmann F, Richmond SA, Mechoulam R, Nadler V, Kloog Y, Sokolovsky M (December 1989).

3944:"Synaptic versus extrasynaptic NMDA receptor signalling: implications for neurodegenerative disorders" 2629:. In addition, ketamine is already employed for this purpose as an off-label therapy in some clinics. 11966: 11677: 9080: 8548:

Kasper S, McEwen BS (2008). "Neurobiological and clinical effects of the antidepressant tianeptine".

7387:"Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation" 2622: 2125:

have been shown to have a similar effect to polyamines, and this may explain their neurotoxic effect.

2020: 1625: 1590: 1151:, where it can act as a coincidence detector for membrane depolarization and synaptic transmission. 981:. Phosphorylation of Jacob does not take place with extrasynaptic NMDA stimulation. This allows the 11881: 10300: 9294: 8833: 8061:"Pharmacologically targeted NMDA receptor antagonism by NitroMemantine for cerebrovascular disease" 6141:

Milnerwood AJ, Gladding CM, Pouladi MA, Kaufman AM, Hines RM, Boyd JD, et al. (January 2010).

5327:"Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists" 2759:

in animals and in patients with brain injury. This use has not been tested in clinical trials yet.

2246: 1621: 1561: 1518: 1422: 1408: 995: 596:

family of GluN3 A and B subunits have an inhibitory effect on receptor activity. Multiple receptor

312: 296: 6497:

J. Moskal, D. Leander, R. Burch (2010). Unlocking the Therapeutic Potential of the NMDA Receptor.

4671:"Core Differences in Synaptic Signaling Between Primary Visual and Dorsolateral Prefrontal Cortex" 12257: 12011: 11734: 11529: 2187:

not only pass through the NMDA receptor channel but also modulate the activity of NMDA receptors.

366: 172:. Activation of NMDA receptors results in the opening of the ion channel that is nonselective to 5915:

Lai TW, Shyu WC, Wang YT (May 2011). "Stroke intervention pathways: NMDA receptors and beyond".

421:

Cartoon representation of the human NMDA receptor. Each subunit is individually rainbow colored.

11927: 11891: 11650: 11613: 11404: 10879: 10672: 10484: 10475: 9481: 2748: 2484: 2335: 2160: 1649: 1644: 1636:

Common agents in which NMDA receptor antagonism is the primary or a major mechanism of action:

1320: 1050: 1017: 639: 362: 358: 350: 5957:

Beesley S, Sullenberger T, Crotty K, Ailani R, D'Orio C, Evans K, et al. (October 2020).

5212:

Gajendran N, Kapfhammer JP, Lain E, Canepari M, Vogt K, Wisden W, Brenner HR (February 2009).

4574: 2678:

Cochlear NMDARs are the target of intense research to find pharmacological solutions to treat

12267: 11707: 11399: 8829: 8525: 8352:

McEwen BS, Chattarji S, Diamond DM, Jay TM, Reagan LP, Svenningsson P, Fuchs E (March 2010).

7385:

Hawasli AH, Benavides DR, Nguyen C, Kansy JW, Hayashi K, Chambon P, et al. (July 2007).

7052:

Glushakov AV, Dennis DM, Morey TE, Sumners C, Cucchiara RF, Seubert CN, Martynyuk AE (2002).

6815:

Monge-Fuentes V, Gomes FM, Campos GA, Silva J, Biolchi AM, Dos Anjos LC, et al. (2015).

6565:"The Bad News Isn't In: A Look at Dissociative-Induced Brain Damage and Cognitive Impairment" 2082: 1778: 663: 268: 103: 27: 7483:

Chen Y, Beffert U, Ertunc M, Tang TS, Kavalali ET, Bezprozvanny I, Herz J (September 2005).

5065:

Sprengel R, Suchanek B, Amico C, Brusa R, Burnashev N, Rozov A, et al. (January 1998).

4718:

Burt JB, Demirtaş M, Eckner WJ, Navejar NM, Ji JL, Martin WJ, et al. (September 2018).

2506:

range to result in negative membrane potential. NMDA receptors are modulated by a number of

638:

contributes residues to the channel pore and is responsible for the receptor's high-unitary

11959: 11784: 11717: 11697: 11692: 10522: 10237: 9978: 9554: 8236: 8196:

Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, McNamara JD, White LE (2008).

8116:

Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, McNamara JD, White LE (2008).

8072: 7895: 7837:

Nelson PA, Sage JR, Wood SC, Davenport CM, Anagnostaras SG, Boulanger LM (September 2013).

7793: 7734: 6914: 5970: 5766:

Papouin T, Ladépêche L, Ruel J, Sacchi S, Labasque M, Hanini M, et al. (August 2012).

5584:

Karpova A, Mikhaylova M, Bera S, Bär J, Reddy PP, Behnisch T, et al. (February 2013).

5067:"Importance of the intracellular domain of NR2 subunits for NMDA receptor function in vivo" 4933: 4829: 4448: 3332: 3079: 2979: 1338: 982: 911:

may play a role in the NMDA receptor maturation by increasing the GluN2B subunit mobility.

827: 654: 573:

the polyamines spermidine and spermine are also modulators for the NMDA receptor channels.

288: 158: 7207:"Minocycline targets multiple secondary injury mechanisms in traumatic spinal cord injury" 8: 11851: 11789: 11739: 10884: 10290: 9717: 9615: 9494: 8783: 8059:

Takahashi H, Xia P, Cui J, Talantova M, Bodhinathan K, Li W, et al. (October 2015).

7721:

Fourgeaud L, Davenport CM, Tyler CM, Cheng TT, Spencer MB, Boulanger LM (December 2010).

6119: 5394:

Hardingham GE, Bading H (February 2003). "The Yin and Yang of NMDA receptor signalling".

4767:

Muntané G, Horvath JE, Hof PR, Ely JJ, Hopkins WD, Raghanti MA, et al. (June 2015).

4437:"Evolutionary mode and functional divergence of vertebrate NMDA receptor subunit 2 genes" 2488: 2350: 2215: 2184: 2136: 1512: 1136: 1066: 957:

In order to support the localization hypothesis, it would be necessary to show differing

397: 135: 11774: 11451: 8240: 8076: 7899: 7797: 7738: 6918: 6903:"Nonpsychotropic cannabinoid acts as a functional N-methyl-D-aspartate receptor blocker" 6564: 6514:

Donello JE, Banerjee P, Li YX, Guo YX, Yoshitake T, Zhang XL, et al. (March 2019).

6083: 6056: 5974: 5768:"Synaptic and extrasynaptic NMDA receptors are gated by different endogenous coagonists" 4937: 4833: 4669:

Yang ST, Wang M, Paspalas CD, Crimins JL, Altman MT, Mazer JA, Arnsten AF (April 2018).

4452: 4392:

Stephenson FA (November 2006). "Structure and trafficking of NMDA and GABAA receptors".

3336: 3083: 2983: 2237:

generally believed that NMDA receptors are modulated by endogenous redox agents such as

1011:

Another factor that seems to affect NMDAR induced toxicity is the observed variation in

928:

NMDA receptors have been implicated by a number of studies to be strongly involved with

11814: 11744: 11712: 11687: 10827: 10822: 10662: 10506: 9588: 9297: 9032: 8841: 8736: 8709: 8685: 8660: 8573: 8426: 8378: 8353: 8336:"From Club to Clinic: Physicians Push Off-Label Ketamine as Rapid Depression Treatment" 8260: 8173: 8148: 8093: 8060: 7962: 7919: 7863: 7838: 7814: 7781: 7757: 7722: 7695: 7670: 7651: 7603: 7576: 7557: 7509: 7484: 7460: 7435: 7411: 7386: 7332: 7320: 7288: 7263:

Lipton SA (October 2007). "Pathologically activated therapeutics for neuroprotection".

7233: 7206: 7182: 7157: 7144: 7029: 7004: 6985: 6843: 6816: 6797: 6753: 6668: 6622: 6540: 6515: 6475: 6450: 6449:

Cao W, Shah HP, Glushakov AV, Mecca AP, Shi P, Sumners C, et al. (December 2009).

6395: 6308: 6265: 6216: 6191: 6172: 5991: 5958: 5892: 5883: 5867: 5843: 5818: 5748: 5736: 5700: 5675: 5651: 5626: 5561: 5536: 5512: 5487: 5463: 5438: 5419: 5351: 5342: 5326: 5238: 5213: 5189: 5164: 5140: 5115: 5096: 5042: 5017: 4993: 4968: 4901: 4876: 4852: 4817: 4793: 4768: 4744: 4719: 4695: 4670: 4646: 4621: 4602: 4519: 4471: 4436: 4417: 4374: 4294: 4269: 4121: 4097:"The lipophilic bullet hits the targets: medicinal chemistry of adamantane derivatives" 4096: 4068: 4017: 3992: 3968: 3943: 3919: 3866: 3841: 3822: 3717: 3705: 3632: 3566: 3514: 3355: 3320: 3319:

Castelli MP, Madeddu C, Casti A, Casu A, Casti P, Scherma M, et al. (2014-05-20).

3296: 3271: 3207: 3103: 3047: 3022: 3003: 2863: 2854: 2838: 2610: 2563: 2303:

receptor by the agonist, i.e. it only enters the channel when it is opened by agonist.

2180: 2152: 2040:

effects. Alkyl nitrates donate NO in the form of a nitro group as seen in figure 7, -NO

1927: 1640: 1598: 628: 177: 169: 79: 7156:

Ludolph AG, Udvardi PT, Schaz U, Henes C, Adolph O, Weigt HU, et al. (May 2010).

6937: 6902: 6741: 6704: 6687: 5407: 5083: 5066: 4945: 4201: 3810: 3774: 3749: 3195: 2808: 2791: 2376:

group is protonated under physiological pH of the body to carry a positive charge, -NH

682:. Channel activation of NMDA receptors is a result of the binding of two co agonists, 11835: 11409: 10315: 10211: 10029: 9922: 9597: 8741: 8690: 8614: 8565: 8561: 8506: 8467: 8418: 8383: 8301: 8252: 8203: 8178: 8123: 8098: 8041: 7999: 7989: 7954: 7950: 7911: 7868: 7819: 7762: 7700: 7643: 7608: 7549: 7514: 7465: 7416: 7367: 7324: 7280: 7238: 7187: 7173: 7116: 7075: 7034: 6977: 6973: 6942: 6883: 6848: 6789: 6745: 6709: 6660: 6614: 6545: 6480: 6466: 6431: 6387: 6352: 6347: 6330: 6300: 6257: 6221: 6164: 6123: 6088: 6037: 5996: 5932: 5897: 5848: 5799: 5740: 5705: 5656: 5607: 5566: 5535:

Xu J, Kurup P, Zhang Y, Goebel-Goody SM, Wu PH, Hawasli AH, et al. (July 2009).

5517: 5468: 5411: 5356: 5307: 5243: 5194: 5145: 5088: 5047: 4998: 4949: 4906: 4857: 4798: 4749: 4700: 4651: 4594: 4555: 4511: 4476: 4409: 4366: 4329: 4299: 4243: 4205: 4167: 4162: 4145: 4126: 4072: 4060: 4022: 3973: 3911: 3871: 3814: 3779: 3709: 3674: 3624: 3558: 3506: 3501: 3484: 3450: 3402: 3360: 3301: 3252: 3199: 3164: 3137: 3095: 3052: 2995: 2944: 2917: 2909: 2868: 2813: 2650: 2587: 2575: 2473: 1582: 1459: 1207: 1037: 978: 963: 236: 8659:

Lisman JE, Coyle JT, Green RW, Javitt DC, Benes FM, Heckers S, Grace AA (May 2008).

8577: 8430: 8414: 7966: 7561: 7336: 7292: 7158:"Atomoxetine acts as an NMDA receptor blocker in clinically relevant concentrations" 6989: 6757: 6672: 6626: 6399: 6312: 6269: 6176: 5423: 5114:

Groc L, Choquet D, Stephenson FA, Verrier D, Manzoni OJ, Chavis P (September 2007).

4606: 4421: 4378: 3826: 3636: 3570: 3518: 3270:

Sánchez-Blázquez P, Rodríguez-Muñoz M, Vicente-Sánchez A, Garzón J (November 2013).

3269: 3211: 2091:– naturally occurring negative allosteric modulators of the polyamine site found in 894:

Increase of GluN2A diluting the number of GluN2B without the decrease of the latter.

12082: 12006: 11901: 11896: 11809: 10964: 10281: 10227: 10005: 9943: 9620: 9339: 9072: 8731: 8721: 8680: 8672: 8604: 8557: 8498: 8457: 8410: 8373: 8365: 8291: 8264: 8244: 8168: 8164: 8160: 8088: 8080: 8033: 7946: 7923: 7903: 7858: 7850: 7809: 7801: 7752: 7742: 7690: 7682: 7655: 7635: 7598: 7588: 7541: 7504: 7500: 7496: 7455: 7451: 7447: 7406: 7398: 7359: 7316: 7272: 7228: 7218: 7177: 7169: 7106: 7065: 7024: 7016: 7005:"Subunit arrangement and phenylethanolamine binding in GluN1/GluN2B NMDA receptors" 6969: 6932: 6922: 6875: 6838: 6828: 6801: 6781: 6737: 6699: 6652: 6604: 6535: 6527: 6470: 6462: 6423: 6379: 6342: 6292: 6249: 6211: 6203: 6154: 6115: 6078: 6068: 6027: 5986: 5978: 5924: 5887: 5879: 5838: 5830: 5789: 5779: 5752: 5732: 5695: 5691: 5687: 5646: 5638: 5597: 5556: 5552: 5548: 5507: 5503: 5499: 5458: 5454: 5450: 5403: 5346: 5338: 5297: 5233: 5229: 5225: 5184: 5180: 5176: 5135: 5131: 5127: 5100: 5078: 5037: 5033: 5029: 4988: 4984: 4980: 4941: 4896: 4892: 4888: 4847: 4837: 4788: 4780: 4739: 4731: 4690: 4682: 4641: 4633: 4586: 4547: 4523: 4503: 4466: 4456: 4401: 4358: 4289: 4281: 4235: 4197: 4157: 4116: 4108: 4052: 4012: 4004: 3963: 3955: 3903: 3861: 3853: 3806: 3769: 3761: 3721: 3701: 3666: 3616: 3550: 3496: 3440: 3394: 3350: 3340: 3291: 3283: 3244: 3191: 3107: 3087: 3042: 3034: 3007: 2987: 2899: 2858: 2850: 2803: 2567: 2469: 2093: 1931: 1710: 1666: 1614: 1601:. NMDA receptor antagonists that have been shown to induce Olney's lesions include 1224: 1213: 1148: 985:

in the nucleus to respond differently based in the phosphorylation state of Jacob.

864:

The timecourse of GluN2B-GluN2A switch in human cerebellum. Bar-Shira et al., 2015

800: 612: 201: 99: 7805: 7135: 6057:"Visualizing the triheteromeric N-methyl-D-aspartate receptor subunit composition" 3923: 1446:, is a weak partial NMDA receptor agonist acting on the glycine site. 3,5-Dibromo- 891:

Extrasynaptic displacement of GluN2B away from the synapse with increase in GluN2A

11866: 11769: 11764: 11464: 11414: 11174: 11094: 11059: 10959: 10400: 10310: 10079: 9655: 8824: 7545: 6159: 6142: 6032: 6015: 5928: 5302: 5285: 4842: 4637: 4620:

Wang M, Yang Y, Wang CJ, Gamo NJ, Jin LE, Mazer JA, et al. (February 2013).

4461: 3345: 2744: 2709: 2328: 1940: 1455: 1393: 1230: 1117: 1036:

Excitotoxicity has been thought to play a role in the degenerative properties of

1012: 846: 675: 650: 378: 316: 260: 38: 8644: 4967:

Liu Y, Wong TP, Aarts M, Rooyakkers A, Liu L, Lai TW, et al. (March 2007).

4551: 3541:

Kemp JA, McKernan RM (November 2002). "NMDA receptor pathways as drug targets".

3385:

Johnson JW, Kotermanski SE (February 2006). "Mechanism of action of memantine".

2036:

Unlike many other NO donors, alkyl nitrates do not have potential NO associated

1107:

for the efficient opening of the ion channel, which is a part of this receptor.

417: 12016: 11996: 11886: 11759: 11754: 11702: 11374: 11354: 11119: 11054: 10974: 10954: 10750: 10222: 10151: 9938: 9857: 8906: 8858: 8676: 8502: 8037: 7727:

Proceedings of the National Academy of Sciences of the United States of America

7593: 7363: 6907:

Proceedings of the National Academy of Sciences of the United States of America

6427: 6207: 6073: 5982: 5784: 5767: 5642: 5627:"Synaptic plasticity of NMDA receptors: mechanisms and functional implications" 5602: 5585: 4239: 3445: 3428: 3398: 3248: 2936: 2904: 2887: 2752: 2736: 2527: 2334:

Memantine is the first drug approved for treatment of severe and more advanced

2260: 2122: 2049: 1790: 1586: 1042: 958: 929: 899: 831: 816: 589: 569: 532: 303: 193: 8726: 7981: 7639: 6833: 5674:

Li S, Jin M, Koeglsperger T, Shepardson NE, Shankar GM, Selkoe DJ (May 2011).

4735: 2636:

produces antidepressant effects through indirect alteration and inhibition of

2229:

The activity of NMDA receptors is also strikingly sensitive to the changes in

932:. Because NMDA receptors play an important role in the health and function of 768:

NR2 subunit in vertebrates (left) and invertebrates (right). Ryan et al., 2008

12251: 11749: 11636: 11544: 11539: 11519: 11379: 11344: 11199: 11194: 11184: 11159: 11154: 11089: 11049: 11009: 10590: 10295: 10207: 10146: 10091: 10059: 9918: 9852: 9672: 9645: 9314: 8898: 8850: 8305: 7780:

Huh GS, Boulanger LM, Du H, Riquelme PA, Brotz TM, Shatz CJ (December 2000).

7223: 7095:"Long-term changes in glutamatergic synaptic transmission in phenylketonuria" 6879: 6296: 5834: 5286:"Extrasynaptic NMDA receptor involvement in central nervous system disorders" 3670: 2913: 2740: 2664: 2654: 2618: 2571: 2555: 2551: 2032: 1989: 1860: 1854: 1848: 1826: 1814: 1773: 1731: 1606: 1492: 1451: 1440: 1308: 1219: 1201: 1180: 1173: 1169: 1097: 1093: 1074: 609: 565: 553:

Transmembrane region of NR1 (left) and NR2B (right) subunits of NMDA receptor

515: 373: 264: 217: 189: 131: 95: 7747: 7723:"MHC class I modulates NMDA receptor function and AMPA receptor trafficking" 7686: 6927: 6283:

Wolosker H (October 2006). "D-serine regulation of NMDA receptor activity".

5819:"Diversity in NMDA receptor composition: many regulators, many consequences" 4784: 4686: 4056: 3765: 3038: 2415: 1589:

properties, in addition to their unique effects at elevated dosages such as

1573:, a synthetic general anesthetic and one of the best-known NMDAR antagonists 1147:, and it has been suggested that this channel is a biochemical substrate of 783:

and are referred to with the nomenclature GluN2A through GluN2D (encoded by

11906: 11856: 11794: 11334: 11164: 11134: 11039: 11004: 10939: 10924: 10702: 10203: 10176: 10131: 9928: 9914: 9882: 9832: 9787: 9502: 8745: 8694: 8618: 8569: 8510: 8471: 8422: 8387: 8182: 8102: 8045: 8003: 7872: 7823: 7766: 7704: 7647: 7612: 7518: 7469: 7420: 7371: 7284: 7242: 7191: 7120: 7111: 7094: 7079: 7038: 6887: 6852: 6793: 6749: 6713: 6664: 6618: 6549: 6484: 6435: 6391: 6383: 6356: 6304: 6261: 6253: 6225: 6168: 6127: 6092: 6041: 6000: 5936: 5901: 5866:

Petralia RS, Wang YX, Hua F, Yi Z, Zhou A, Ge L, et al. (April 2010).

5852: 5803: 5744: 5709: 5660: 5611: 5570: 5521: 5472: 5415: 5311: 5247: 5198: 5149: 5051: 5002: 4953: 4910: 4861: 4818:"Gene Expression Switching of Receptor Subunits in Human Brain Development" 4802: 4753: 4704: 4655: 4598: 4559: 4515: 4480: 4435:

Teng H, Cai W, Zhou L, Zhang J, Liu Q, Wang Y, et al. (October 2010).

4413: 4370: 4303: 4247: 4209: 4171: 4130: 4064: 4026: 3977: 3915: 3875: 3857: 3818: 3783: 3713: 3678: 3628: 3562: 3510: 3454: 3406: 3364: 3305: 3256: 3203: 3168: 3141: 3056: 2999: 2948: 2921: 2702: 2579: 2324: 2311: 2291: 2190: 1995: 1985: 1975: 1594: 1500: 1385: 1335:(neboglamine) – synthetic positive allosteric modulator of the glycine site 773: 536: 402: 332:

The discovery of NMDA receptors was followed by the synthesis and study of

302:

Overactivation of the receptor, causing excessive influx of Ca can lead to

276: 256: 185: 8462: 8445: 8256: 7958: 7915: 7854: 7782:"Functional requirement for class I MHC in CNS development and plasticity" 7553: 7328: 7070: 7053: 6981: 6946: 6785: 6531: 5360: 5092: 4494:

Ryan TJ, Grant SG (October 2009). "The origin and evolution of synapses".

4268:

Limapichat W, Yu WY, Branigan E, Lester HA, Dougherty DA (February 2013).

3429:"Management of moderate to severe Alzheimer's disease: focus on memantine" 3287: 3099: 2872: 2817: 1465:

Other partial agonists of the NMDA receptor acting on novel sites such as

1088:, the major endogenous agonist of the glycine co-agonist site of the NMDAR 12001: 11982: 11830: 11799: 11779: 11524: 11509: 11489: 11459: 11389: 11273: 11253: 11243: 11238: 11218: 11179: 11129: 11124: 11109: 11099: 11064: 11014: 10984: 10979: 10969: 10889: 10832: 10785: 10717: 10692: 10640: 10555: 10441: 10379: 10356: 10064: 10049: 9995: 9983: 9797: 9772: 9660: 9635: 8825: 7669:

Neal AP, Stansfield KH, Worley PF, Thompson RE, Guilarte TR (July 2010).

5794: 4008: 2614: 2602: 2388: 2357:

Structure activity relationship (SAR) of amantadine and related compounds

2275: 2242: 2238: 2164: 2045: 2007: 1967: 1962: 1958: 1909: 1878: 1842: 1761: 1743: 1737: 1725: 1719: 1714: 1679: 1610: 1542: 1488: 1470: 1314: 898:

The GluN2B and GluN2A subunits also have differential roles in mediating

878: 808: 519: 308: 240: 205: 83: 8707: 8296: 8279: 8213: 8133: 7020: 3485:"The chemical biology of clinically tolerated NMDA receptor antagonists" 3321:"Δ9-tetrahydrocannabinol prevents methamphetamine-induced neurotoxicity" 2991: 1376:

Chemical structure of neramexane, second generation memantine derivative

11804: 11562: 11534: 11484: 11469: 11446: 11441: 11436: 11369: 11339: 11329: 11268: 11204: 11189: 11169: 11114: 11084: 11069: 11044: 11029: 10994: 10989: 10949: 10944: 10914: 10899: 10859: 10837: 10800: 10770: 10755: 10735: 10493: 10463: 10446: 10436: 10191: 10181: 10156: 10111: 9988: 9973: 9968: 9948: 9907: 9897: 9887: 9867: 9862: 9822: 9817: 9777: 9767: 9752: 9692: 9667: 8609: 8592: 8369: 4405: 4225: 3155:

Liu Y, Zhang J (October 2000). "Recent development in NMDA receptors".

2837:

Anson LC, Chen PE, Wyllie DJ, Colquhoun D, Schoepfer R (January 1998).

2755:

used in small doses to avoid sedation, but NMDAR antagonists can block

2728: 2724: 2683: 2633: 2606: 2598: 2594: 2583: 2547: 2543: 2515: 2507: 2503: 2499: 2264: 2170: 2111: 2088: 2037: 2011: 1952: 1944: 1895: 1872: 1796: 1767: 1755: 1701: 1578: 1548: 1536: 1466: 1381: 1349: 1332: 1264: 1163: 1101: 1077:(glutamate), the major endogenous agonist of the main site of the NMDAR 884:

There are three hypothetical models to describe this switch mechanism:

812: 780: 706: 578: 393: 150: 8084: 6821:

The Journal of Venomous Animals and Toxins Including Tropical Diseases

4590: 4285: 4112: 2071:

group that leads to second generation memantine analog, nitromemantine

1664:– naturally occurring dizocilpine or related site antagonist found in 1081: 649:, which contain residues that can be directly modified by a series of 503: 11359: 11349: 11307: 11233: 11223: 11149: 11144: 11104: 11079: 11074: 11024: 10999: 10929: 10904: 10894: 10869: 10864: 10854: 10730: 10615: 10600: 10580: 10565: 10560: 10451: 10276: 10271: 10217: 10106: 10101: 10096: 10054: 9963: 9958: 9933: 9842: 9782: 9762: 9757: 9747: 9737: 9712: 9640: 9602:

Tooltip α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor

8248: 7907: 7574: 7434:

Zhang S, Edelmann L, Liu J, Crandall JE, Morabito MA (January 2008).

5959:"D-serine mitigates cell loss associated with temporal lobe epilepsy" 3091: 2720: 2705: 2660: 2523: 2511: 2142: 2115: 2001: 1899: 1820: 1808: 1802: 1749: 1685: 1273: 904: 849: 804: 717: 710: 687: 321: 292: 272: 209: 122: 46: 42: 7276: 6656: 6609: 6593:"Trial watch: phase II boost for glutamate-targeted antidepressants" 6592: 6369: 4507: 4362: 3959: 3620: 2135:-containing NMDA receptors on the synaptic membrane, thus affecting 134:. The NMDA receptor is thought to be very important for controlling 11667: 11504: 11302: 11209: 11034: 11019: 10934: 10849: 10765: 10655: 10537: 10468: 10458: 10320: 10186: 10084: 9892: 7402: 6900: 2732: 2691: 2679: 2539: 2219: 2054: 2016: 1981: 1948: 1866: 1784: 1655: 1602: 1570: 1355: 1144: 1110: 962:

location of the signal origin. Many of these pathways use the same

776: 746:

GluN1-1a, GluN1-1b; GluN1-1a is the most abundantly expressed form.

702: 642:, high-calcium permeability, and voltage-dependent magnesium block. 558: 546: 540: 406: 354: 213: 139: 115: 6866:

Pop E (September 2000). "Nonpsychotropic synthetic cannabinoids".

6412: 3907: 3554: 2279:

pathological areas, because healthy areas contain lower levels of

1704:(NPS-1506) – dizocilpine or related site antagonist; derived from 1120:, and is enriched in the same areas as NMDA receptors. Removal of 33: 11548: 11394: 11384: 11364: 11319: 10805: 10420: 10405: 10371: 10305: 10196: 10074: 9792: 9722: 9702: 9650: 9429: 9424: 9173: 7092: 2888:"Structure, function, and pharmacology of NMDA receptor channels" 2280: 2060: 1936: 1418:(NMDA), a synthetic partial agonist of the main site of the NMDAR 1389: 1268: 1255: 1248: 1244: 1238: 1104: 1085: 941: 843: 819: 683: 597: 527: 523: 225: 221: 197: 154: 111: 50: 11605: 6140: 2617:(CERC-301, MK-0657), are under development for the treatment of 1918: 1439:-phenylalanine, a naturally occurring halogenated derivative of 11661: 11424: 11324: 10697: 10428: 10410: 10387: 9682: 9677: 9419: 9414: 9409: 9404: 9399: 9394: 9193: 9188: 9183: 9178: 9168: 9163: 9158: 9153: 9148: 9143: 9138: 9133: 9057: 9049: 9041: 9002: 8994: 8986: 8978: 8970: 8962: 8954: 8946: 8938: 8930: 8922: 8762: 8321:"Growing Evidence That A Party Drug Can Help Severe Depression" 5956: 5211: 4319:"Chapter 16: Anesthetic agents: General and local anesthetics." 2668: 2519: 2223: 2194: 2176: 2148: 1691: 1506: 1290: 1283: 1279: 1140: 933: 908: 873: 869: 835: 796: 792: 788: 784: 779:, four distinct isoforms of the GluN2 subunit are expressed in 698: 617: 490: 484: 473: 467: 461: 455: 233: 143: 127: 87: 16:

Glutamate receptor and ion channel protein found in nerve cells

11951: 8195: 8115: 3123: 2885: 2318:

Chemical structures of memantine (right) and amantadine (left)

1498:) – naturally occurring glycine site partial agonist found in 1028:-NMDA receptors has recently been visualized in brain tissue. 392:

A fortuitous finding was made in 1968 when a woman was taking

11419: 10844: 10635: 10361: 10171: 9697: 9687: 9537: 9532: 9527: 9522: 9517: 9512: 9507: 9462: 9454: 9389: 9364: 9359: 9354: 9349: 9344: 9333: 9328: 9323: 9318: 9203: 9198: 9104: 9096: 9088: 9025: 9020: 9015: 9010: 8886: 8881: 8876: 8871: 8866: 8226: 7988:. Frontiers in Neuroscience. Boca Raton, Florida: CRC Press. 7485:"Reelin modulates NMDA receptor activity in cortical neurons" 6814: 4270:"Key binding interactions for memantine in the NMDA receptor" 2559: 2424:(SAR) of these novel drugs. One class, containing a nitro (NO 2211: 1884: 1836: 1369: 940:

has more to do with excitotoxicity than stimulation of their

839: 739: 735: 581:

are also exclusively displayed by the GluN1/GluN2B receptor.

446: 252: 9584: 7720: 7668: 7305: 6238: 5113: 4536: 4042: 3124:

Dingledine R, Borges K, Bowie D, Traynelis SF (March 1999).

2790:

Laube B, Hirai H, Sturgess M, Betz H, Kuhse J (March 1997).

811:, and contains the binding-site for the selective inhibitor 616:

contains two globular structures: a modulatory domain and a

11312: 11139: 10725: 10712: 10346: 10166: 10136: 10126: 10039: 9872: 9837: 9827: 9625: 9112: 7384: 7051: 6770: 6726: 5868:"Organization of NMDA receptors at extrasynaptic locations" 5673: 5486:

Wang Y, Briz V, Chishti A, Bi X, Baudry M (November 2013).

3069: 2969: 2392: 2286: 2253: 2200: 2156: 2132: 2128: 1857:- a naturally occurring amino acid, glycine site antagonist 1566: 593: 346: 229: 20: 12163:

Nucleoside and nucleotide reverse-transcriptase inhibitors

5765: 5064: 4267: 564:

or glycine binding at its GluN1-linked binding site and

255:

protein to counteract the toxic effects of NMDAR-mediated

10550: 8351: 7002: 6959: 4717: 3181: 2642: 2416:

Second generation derivative of memantine; nitromemantine

1776:– naturally occurring glutamate site antagonist found in 1673: 888:

Increase in synaptic GluN2A along with decrease in GluN2B

173: 8146: 8058: 7433: 7155: 6642: 5816: 5583: 5534: 3893: 3318: 2836: 2735:

have been extensively investigated for the treatment of

2345: 2270: 1581:

for animals and sometimes humans, and are often used as

1329:(DHEA-S) – endogenous weak positive allosteric modulator 8327: 8280:"Emerging Therapies for Treatment Resistant Depression" 7836: 4668: 2479:

Therefore, the NMDA receptor functions as a "molecular

2331:

but was later found to be an NMDA receptor antagonist.

2230: 1404: 1031: 10842:

Uncompetitive pore blockers (mostly dizocilpine site):

8658: 8202:(4th ed.). Sinauer Associates. pp. 191–195. 8122:(4th ed.). Sinauer Associates. pp. 129–131. 7779: 5817:

Sanz-Clemente A, Nicoll RA, Roche KW (February 2013).

4966: 3427:

Dominguez E, Chin TY, Chen CP, Wu TY (December 2011).

2789: 2663:, a low-trapping NMDAR antagonist, is approved in the 1384:

which was discovered by studying number of aminoalkyl

1323:(DHEA) – endogenous weak positive allosteric modulator 1222:– naturally occurring glutamate site agonist found in 949:

mechanisms is known as the "localization hypothesis".

12108:

Dual serotonin and norepinephrine reuptake inhibitors

10248: 7482: 6638: 6636: 6448: 5577: 3691: 1396:

for four indications, including Alzheimer's disease.

1276:(monomethylglycine) – endogenous glycine site agonist 8023: 7936: 6859: 6556: 6520:

The International Journal of Neuropsychopharmacology

6513: 5759: 4924:

Tsien JZ (April 2000). "Building a brainier mouse".

4815: 4766: 9493: 7885: 7531: 4573:Bunk EC, König HG, Prehn JH, Kirby BP (June 2014). 4572: 4328:. Philadelphia: Lippincott Williams & Wilkins. 4094: 3426: 3230:"NMDA receptor subunits: function and pharmacology" 1539:(AGN-241751) - synthetic novel site partial agonist 994:of LTP can be prevented with the introduction of a 259:production and zinc release. As well as preventing 6633: 6192:"Ion Channel Functions in Early Brain Development" 6054: 6020:Biochimica et Biophysica Acta (BBA) - Biomembranes 6013: 5437:Xia P, Chen HS, Zhang D, Lipton SA (August 2010). 5436: 3384: 2502:range while intracellular magnesium ions are at a 2306: 830:, and mediate higher cognitive operations such as 8140: 7003:Karakas E, Simorowski N, Furukawa H (June 2011). 5865: 5485: 2673:National Institute for Health and Care Excellence 2514:compounds and play a key role in a wide range of 2366:Three-ring structure with a bridgehead amine, -NH 1545:(NRX-1074) – synthetic novel site partial agonist 1528:(NMDA) – synthetic glutamate site partial agonist 1233:(quinolinate) – endogenous glutamate site agonist 1092:Activation of NMDA receptors requires binding of 184:Activity of the NMDA receptor is blocked by many 168:(NMDA) binds selectively to it, and not to other 12249: 8625: 8484: 7716: 7714: 6688:"Is agmatine a novel neurotransmitter in brain?" 5393: 4816:Bar-Shira O, Maor R, Chechik G (December 2015). 4619: 4434: 3941: 3433:Taiwanese Journal of Obstetrics & Gynecology 1923:Tooltip attention-deficit hyperactivity disorder 1713:(DXM) – dizocilpine site antagonist; prodrug of 1551:(GLYX-13) – synthetic novel site partial agonist 1204:(glutamate) – endogenous glutamate site agonist 1186:) – endogenous glutamate site agonist. The word 1045:. D-serine, an antagonist/inverse co-agonist of 944:counterparts. In addition, while stimulation of 12153:Non-nucleoside reverse-transcriptase inhibitors 8400: 7625: 6014:Fourie C, Li D, Montgomery JM (February 2014). 4385: 3889: 3887: 3885: 3796: 3656: 3223: 3221: 2943:, Treasure Island (FL): StatPearls Publishing, 2675:for patients who fail other treatment options. 2085:– endogenous weak negative allosteric modulator 1643:(AV-101) – glycine site antagonist; prodrug of 1341:– endogenous weak positive allosteric modulator 1317:– endogenous weak positive allosteric modulator 1311:– endogenous weak positive allosteric modulator 10500: 10485: 8271: 8189: 8109: 6685: 5283: 4874: 4221: 4219: 4187: 3227: 3119: 3117: 2593:NMDAR-targeted compounds, including ketamine, 2110:The NMDA receptor is modulated by a number of 1906:drug; low-trapping dizocilpine site antagonist 1698:-NMDA receptor antagonist / inverse co-agonist 1485:(ACC) – synthetic glycine site partial agonist 11967: 11621: 9570: 8810: 8652: 8645:https://doi.org/10.1016/S1474-4422(16)30043-6 8485:Brink CB, Harvey BH, Brand L (January 2006). 8478: 8437: 8394: 8147:Vargas-Caballero M, Robinson HP (July 2004). 8019: 8017: 8015: 8013: 7773: 7711: 7476: 7427: 7378: 7352:Journal of Molecular Graphics & Modelling 7343: 6586: 6584: 6105: 5324: 4351:International Journal of Geriatric Psychiatry 4348: 4263: 4261: 4259: 4257: 1577:Antagonists of the NMDA receptor are used as 1509:– synthetic glycine site weak partial agonist 1267:– synthetic glycine site agonist; prodrug of 1006: 952: 90:. The NMDA receptor is one of three types of 19:"NR1" redirects here. For the submarine, see 8590: 8547: 8543: 8541: 7979: 7930: 7525: 7349: 7198: 7045: 6996: 6808: 6764: 6720: 6679: 6328: 6276: 6232: 6134: 5908: 5859: 5667: 5624: 5528: 5479: 5430: 5205: 5156: 5107: 5009: 4960: 4917: 4875:Liu XB, Murray KD, Jones EG (October 2004). 4868: 4809: 4530: 4428: 4143: 3882: 3685: 3540: 3422: 3420: 3418: 3416: 3218: 3175: 2769:Calcium/calmodulin-dependent protein kinases 2428:) group opposite to the bridgehead amine (NH 1955:used recreationally; unknown site antagonist 1194:-aspartate (NMDA) is partially derived from 738:subunit produced by alternative splicing of 387:NMDAR/TRPM4 interaction interface inhibitors 102:. Depending on its subunit composition, its 8631:NICE technology appraisal January 18, 2011 8584: 7299: 7204: 6953: 6894: 5914: 5716: 5373: 5318: 5162: 4760: 4216: 4095:Wanka L, Iqbal K, Schreiner PR (May 2013). 3839: 3602: 3600: 3148: 3114: 3014: 2934: 1159:Some known NMDA receptor agonists include: 385:form a death signaling complex with TRPM4. 11974: 11960: 11628: 11614: 11587:Metabotropic glutamate receptor modulators 9577: 9563: 8817: 8803: 8513:. Archived from the original on 2013-04-14 8443: 8277: 8052: 8010: 7258: 7256: 7254: 7252: 6581: 6189: 5325:Choi DW, Koh JY, Peters S (January 1988). 5015: 4391: 4254: 3743: 3741: 3739: 3737: 3735: 3733: 3731: 3598: 3596: 3594: 3592: 3590: 3588: 3586: 3584: 3582: 3580: 3482: 3380: 3378: 3376: 3374: 3063: 2965: 2963: 2935:Jewett, Benjamin E.; Thapa, Bicky (2024), 2443: 2398:of (2.3+0.3) μM while amantadine has an IC 1811:– low-trapping dizocilpine site antagonist 1799:– low-trapping dizocilpine site antagonist 1515:– synthetic glutamate site partial agonist 914: 855: 11594:Glutamate metabolism/transport modulators 8735: 8725: 8684: 8608: 8538: 8461: 8377: 8347: 8345: 8295: 8172: 8092: 7973: 7862: 7813: 7756: 7746: 7694: 7602: 7592: 7508: 7459: 7410: 7232: 7222: 7181: 7110: 7069: 7028: 6936: 6926: 6842: 6832: 6703: 6608: 6539: 6474: 6346: 6215: 6158: 6082: 6072: 6031: 5990: 5891: 5842: 5793: 5783: 5722: 5699: 5650: 5601: 5560: 5511: 5462: 5350: 5301: 5237: 5188: 5139: 5082: 5041: 4992: 4900: 4851: 4841: 4792: 4743: 4694: 4645: 4493: 4470: 4460: 4293: 4183: 4181: 4161: 4120: 4016: 3967: 3865: 3773: 3500: 3444: 3413: 3354: 3344: 3295: 3046: 2903: 2862: 2807: 2647:Tooltip brain-derived neurotrophic factor 923: 772:While a single GluN2 subunit is found in 10006: 8593:"Alzheimer disease: progress or profit?" 8312: 6562: 6282: 4711: 4662: 4613: 4566: 4487: 4326:Foye's Principles of Medicinal Chemistry 4090: 4088: 4086: 4084: 4082: 3942:Hardingham GE, Bading H (October 2010). 3154: 2533: 2349: 2310: 2290: 2287:Noncompetitive NMDA receptor antagonists 2254:Development of NMDA receptor antagonists 2059: 1565: 1532:Positive allosteric modulators include: 1403: 1368: 1080: 1065: 859: 763: 545: 522:protein receptor that is activated when 502: 416: 32: 12113:Selective serotonin reuptake inhibitors 7249: 3833: 3728: 3652: 3650: 3648: 3646: 3577: 3536: 3534: 3532: 3530: 3528: 3478: 3476: 3474: 3472: 3470: 3468: 3466: 3464: 3371: 3020: 2960: 2832: 2830: 2785: 2783: 2653:. Tianeptine also acts on the NMDA and 2173:kinase enhances NMDA receptor currents. 12250: 11317:Alcohols/volatile anesthetics/related: 8342: 7262: 6590: 6055:Beesley S, Gunjan A, Kumar SS (2023). 5279: 5277: 4342: 4178: 3990: 3747: 3606: 3228:Paoletti P, Neyton J (February 2007). 2459: 1746:(MK-801) – dizocilpine site antagonist 1658:– endogenous polyamine site antagonist 1380:An example of memantine derivative is 669: 340:-aspartic acid (NMDA) in the 1960s by 11955: 11609: 10473:Other positive allosteric modulators: 10253:Tooltip N-Methyl-D-aspartate receptor 9558: 8798: 6500:Drug Discovery & Development News 6329:Beesley S, Kumar SS (November 2023). 6324: 6322: 5952: 5950: 5948: 5946: 5389: 5387: 5385: 5284:Parsons MP, Raymond LA (April 2014). 5275: 5273: 5271: 5269: 5267: 5265: 5263: 5261: 5259: 5257: 4923: 4316: 4310: 4144:Beesley S, Kumar SS (November 2023). 4079: 4038: 4036: 3937: 3935: 3933: 3790: 3126:"The glutamate receptor ion channels" 2714:glutamate hypothesis of schizophrenia 2346:Structure activity relationship (SAR) 2271:Competitive NMDA receptor antagonists 1728:– dizocilpine-related site antagonist 1454:, and neurological disorders such as 239:, an effect known to be prevented by 232:, which significantly contributes to 11934: 8491:Recent Patents on CNS Drug Discovery 8333: 8318: 6416:Recent Patents on CNS Drug Discovery 6190:Smith RS, Walsh CA (February 2020). 6120:10.1001/archopht.1957.00940010205006 3997:The Journal of Experimental Medicine 3840:Watkins JC, Jane DE (January 2006). 3643: 3525: 3461: 2827: 2780: 2682:. NMDARs are associated with a rare 1793:– endogenous glycine site antagonist 1032:Excitotoxicity in a clinical setting 988: 826:, GluN2B are exclusively within the 803:. They contain the binding-site for 11214:Ifenprodil (NR2B) site antagonists: 6865: 4324:. In Lemke TL, Williams DA (eds.). 3027:The New England Journal of Medicine 2031:The NMDA receptor is regulated via 2019:– an atypical opioid analgesic and 1851:(PCP) – dizocilpine site antagonist 1722:(DXO) – dizocilpine site antagonist 1399: 1358:– endogenous polyamine site agonist 1352:– endogenous polyamine site agonist 1296:) – endogenous glycine site agonist 1261:) – endogenous glycine site agonist 1216:– endogenous glutamate site agonist 920:through ErbB2 and ErbB4 receptors. 13: 12203:Bcr-Abl tyrosine-kinase inhibitors 9778:Pesampator (BIIB-104, PF-04958242) 7321:10.1111/j.1471-4159.1992.tb08468.x 6692:Trends in Pharmacological Sciences 6686:Reis DJ, Regunathan S (May 2000). 6319: 6061:Frontiers in Synaptic Neuroscience 6007: 5943: 5884:10.1016/j.neuroscience.2010.01.022 5737:10.1016/j.brainresbull.2012.12.003 5625:Hunt DL, Castillo PE (June 2012). 5382: 5343:10.1523/JNEUROSCI.08-01-00185.1988 5254: 4033: 3930: 3706:10.1016/j.neuroscience.2005.10.014 3276:Antioxidants & Redox Signaling 2855:10.1523/JNEUROSCI.18-02-00581.1998 2696:anti-glutamate receptor antibodies 1241:– endogenous glycine site agonist 1210:– synthetic glutamate site agonist 14: 12294: 12218:Neurokinin 1 receptor antagonists 12093:Dipeptidyl peptidase-4 inhibitors 11635: 8755: 5163:Espinosa JS, Luo L (March 2008). 4946:10.1038/scientificamerican0400-62 2640:receptor activity and release of 2466:excitatory postsynaptic potential 2214:trafficking and NMDAR-dependent 2026: 1914:norepinephrine reuptake inhibitor 1392:as memantine. Neramexane went to 12208:Cannabinoid receptor antagonists 11933: 11922: 11921: 8761: 8701: 8637: 8591:Mount C, Downton C (July 2006). 8562:10.2165/00023210-200822010-00002 8444:McEwen BS, Olié JP (June 2005). 8403:European Neuropsychopharmacology 8220: 7982:"Pharmacology of NMDA Receptors" 7879: 7830: 7662: 7619: 7581:Cell Communication and Signaling 7568: 7174:10.1111/j.1476-5381.2010.00707.x 6467:10.1111/j.1476-5381.2009.00498.x 6348:10.1016/j.neuropharm.2023.109654 6108:A.M.A. Archives of Ophthalmology 4579:Journal of Neuroscience Research 4394:Biochemical Society Transactions 4163:10.1016/j.neuropharm.2023.109654 3502:10.1111/j.1471-4159.2006.03991.x 3483:Chen HS, Lipton SA (June 2006). 2719:NMDAR antagonists, for instance 2208:major histocompatibility complex 2151:modulates NMDA function through 1483:Aminocyclopropanecarboxylic acid 734:There are eight variants of the 243:, mediated by activation of the 12037:and development of drug classes 11981: 11678:Central pattern generator (CPG) 11254:Rislenemdaz (CERC-301, MK-0657) 10201:Negative allosteric modulators: 10089:Positive allosteric modulators: 9912:Negative allosteric modulators: 9665:Positive allosteric modulators: 8415:10.1016/j.euroneuro.2004.09.008 7205:Shultz RB, Zhong Y (May 2017). 7162:British Journal of Pharmacology 7127: 7086: 6569:Erowid DXM Vaults : Health 6507: 6491: 6455:British Journal of Pharmacology 6442: 6406: 6363: 6183: 6099: 6048: 5810: 5631:Current Opinion in Neurobiology 5618: 5367: 5058: 5016:Zhou M, Baudry M (March 2006). 4228:Current Opinion in Pharmacology 4190:Pharmacology & Therapeutics 4137: 3984: 3846:British Journal of Pharmacology 3387:Current Opinion in Pharmacology 3312: 3263: 3237:Current Opinion in Pharmacology 3184:Current Opinion in Neurobiology 3023:"Memory and the NMDA receptors" 2688:anti-NMDA receptor encephalitis 2566:. These and similar drugs like 2422:structure activity relationship 2307:Memantine and related compounds 12273:Ionotropic glutamate receptors 11872:Frog hearing and communication 10490:Tooltip Dehydroepiandrosterone 9798:Tulrampator (S-47445, CX-1632) 9693:Farampator (CX-691, ORG-24448) 8165:10.1523/jneurosci.1380-04.2004 7501:10.1523/JNEUROSCI.1951-05.2005 7452:10.1523/JNEUROSCI.1900-07.2008 6645:Nature Reviews. Drug Discovery 6597:Nature Reviews. Drug Discovery 5692:10.1523/JNEUROSCI.0203-11.2011 5553:10.1523/JNEUROSCI.2212-09.2009 5504:10.1523/JNEUROSCI.3293-13.2013 5455:10.1523/JNEUROSCI.2488-10.2010 5376:Handbook of Clinical Neurology 5230:10.1523/JNEUROSCI.4303-08.2009 5181:10.1523/JNEUROSCI.5157-07.2008 5132:10.1523/JNEUROSCI.1772-07.2007 5034:10.1523/JNEUROSCI.4299-05.2006 4985:10.1523/JNEUROSCI.0116-07.2007 4893:10.1523/JNEUROSCI.2476-04.2004 3609:Nature Reviews. Drug Discovery 2928: 2879: 2627:treatment-resistant depression 2391:measurements memantine has an 2076:Negative allosteric modulators 1972:acetylcholinesterase inhibitor 1833:O) – undefined site antagonist 1555: 1327:Dehydroepiandrosterone sulfate 1304:Positive allosteric modulators 824:dorsolateral prefrontal cortex 645:Each subunit has an extensive 372:In 2002, it was discovered by 130:(cations) to flow through the 92:ionotropic glutamate receptors 1: 12054:Angiotensin receptor blockers 11580:Receptor/signaling modulators 11429:Unknown/unsorted antagonists: 9993:Unknown/unsorted antagonists: 9586:Ionotropic glutamate receptor 7980:Monaghan DT, Jane DE (2009). 7806:10.1126/science.290.5499.2155 6868:Current Pharmaceutical Design 6742:10.1016/s0006-8993(02)03198-0 6705:10.1016/s0165-6147(00)01460-7 5408:10.1016/s0166-2236(02)00040-1 5084:10.1016/S0092-8674(00)80921-6 4202:10.1016/s0163-7258(02)00302-9 3811:10.1016/S0301-0082(99)00007-6 3659:Current Pharmaceutical Design 3196:10.1016/S0959-4388(00)00215-4 2809:10.1016/S0896-6273(00)81249-0 2774: 2450:amyotrophic lateral sclerosis 2245:, and the essential nutrient 2105: 2100: 1875:– dizocilpine site antagonist 1817:– dizocilpine site antagonist 1787:– dizocilpine site antagonist 1758:– dizocilpine site antagonist 1740:– dizocilpine site antagonist 1631: 1476: 1364: 822:in the newly evolved primate 295:has been recognized to be an 279:is likely to occur through a 12263:Glutamate (neurotransmitter) 7986:Biology of the NMDA Receptor 7951:10.1016/0896-6273(89)90310-3 7546:10.1126/science.275.5300.674 7265:Nature Reviews. Neuroscience 7211:Neural Regeneration Research 6974:10.1016/0006-8993(93)90804-v 6160:10.1016/j.neuron.2010.01.008 6033:10.1016/j.bbamem.2013.03.015 5929:10.1016/j.molmed.2010.12.008 5917:Trends in Molecular Medicine 5303:10.1016/j.neuron.2014.03.030 4843:10.1371/journal.pcbi.1004559 4638:10.1016/j.neuron.2012.12.032 4496:Nature Reviews. Neuroscience 4462:10.1371/journal.pone.0013342 3948:Nature Reviews. Neuroscience 3346:10.1371/journal.pone.0098079 3021:Li F, Tsien JZ (July 2009). 1881:– ifenprodil site antagonist 1770:– ifenprodil site antagonist 1752:– ifenprodil site antagonist 946:extrasynaptic NMDA receptors 938:extrasynaptic NMDA receptors 412: 405:drug, but it showed no such 383:Extrasynaptic NMDA receptors 7: 12232:Melatonin receptor agonists 12183:Thalidomide and its analogs 12138:Memantine and related drugs 12088:Cyclooxygenase 2 inhibitors 11278:NR2A-selective antagonists: 10810:Polyamine site antagonists: 10035:Acromelic acid (acromelate) 9621:Acromelic acid (acromelate) 8153:The Journal of Neuroscience 7489:The Journal of Neuroscience 7440:The Journal of Neuroscience 6591:Flight MH (December 2013). 6504:Retrieved 19 December 2013. 5680:The Journal of Neuroscience 5541:The Journal of Neuroscience 5492:The Journal of Neuroscience 5443:The Journal of Neuroscience 5331:The Journal of Neuroscience 5218:The Journal of Neuroscience 5169:The Journal of Neuroscience 5120:The Journal of Neuroscience 5022:The Journal of Neuroscience 4973:The Journal of Neuroscience 4881:The Journal of Neuroscience 4552:10.1016/j.yexcr.2008.06.009 2937:"Physiology, NMDA Receptor" 2843:The Journal of Neuroscience 2762: 2751:, but were unsuccessful in 1869:– glutamate site antagonist 1863:– undefined site antagonist 1845:– glutamate site antagonist 1839:– glutamate site antagonist 1823:– glutamate site antagonist 1805:– glutamate site antagonist 1764:– undefined site antagonist 1688:– glutamate site antagonist 1682:– glutamate site antagonist 1676:– glutamate site antagonist 1620:Most NMDAR antagonists are 1166:and amino acid derivatives 1154: 1061: 959:cellular signaling pathways 724: 10: 12299: 12098:Direct thrombin inhibitors 12035:Case studies of discovery 11877:Infrared sensing in snakes 11862:Jamming avoidance response 9718:Hydrochlorothiazide (HCTZ) 8774:NMDA receptor pharmacology 8677:10.1016/j.tins.2008.02.005 8503:10.2174/157488906775245327 8038:10.1016/j.phrs.2004.05.005 7984:. In Van Dongen AM (ed.). 7628:Journal of Neurophysiology 7594:10.1186/s12964-021-00813-z 7364:10.1016/j.jmgm.2004.11.006 6428:10.2174/157488906778773706 6208:10.1016/j.tins.2019.12.004 6074:10.3389/fnsyn.2023.1156777 5983:10.1038/s41467-020-18757-2 5785:10.1016/j.cell.2012.06.029 5643:10.1016/j.conb.2012.01.007 5603:10.1016/j.cell.2013.02.002 4822:PLOS Computational Biology 4540:Experimental Cell Research 4240:10.1016/j.coph.2006.08.013 3748:Lipton SA (January 2004). 3446:10.1016/j.tjog.2011.10.004 3399:10.1016/j.coph.2005.09.007 3249:10.1016/j.coph.2006.08.011 2905:10.33549/physiolres.932678 2496:resting-membrane potential 2159:. significantly enhancing 1559: 1056: 1007:Role of differing subunits 979:transported to the nucleus 953:Differing cascade pathways 588:The NMDA receptor forms a 327: 25: 18: 12283:NMDA receptor antagonists 12213:CCR5 receptor antagonists 12034: 11989: 11917: 11844: 11823: 11727: 11643: 11571: 10660:Glycine site antagonists: 10246: 10004: 9595: 9480: 9440: 9377:Voltage- and ligand-gated 9375: 9305: 9293: 9271: 9121: 9071: 8897: 8849: 8840: 8834:ligand-gated ion channels 8727:10.1186/s13054-019-2711-3 8530:: CS1 maint: unfit URL ( 7640:10.1152/jn.2001.86.4.1652 7309:Journal of Neurochemistry 6834:10.1186/s40409-015-0031-x 6563:Anderson C (2003-06-01). 4736:10.1038/s41593-018-0195-0 4274:ACS Chemical Neuroscience 3489:Journal of Neurochemistry 2757:Spreading Depolarizations 2623:major depressive disorder 2021:serotonin releasing agent 1887:– unknown site antagonist 1734:– unknown site antagonist 1652:– glycine site antagonist 498: 369:and other CNS disorders. 313:NMDA receptor antagonists 12148:Neuraminidase inhibitors 11882:Caridoid escape reaction 10548:Competitive antagonists: 10456:Polyamine site agonists: 10442:Neboglamine (nebostinel) 10011:Tooltip Kainate receptor 8026:Pharmacological Research 7224:10.4103/1673-5374.206633 6880:10.2174/1381612003399446 6297:10.1126/stke.3562006pe41 5835:10.1177/1073858411435129 3799:Progress in Neurobiology 3671:10.2174/1381612043386392 2586:effects and are used as 2412:value of (28.4+1.4) μM. 2247:pyrroloquinoline quinone 2131:regulates the amount of 2067:Nitroglycerin donate ONO 1984:– a naturally occurring 1970:– a naturally occurring 1562:NMDA receptor antagonist 1501:Streptomyces orchidaceus 759: 729: 297:uncompetitive antagonist 287:dependent mechanism for 26:Not to be confused with 12123:HIV-protease inhibitors 12044:5α-Reductase inhibitors 11735:Theodore Holmes Bullock 11530:Pentamidine isethionate 11274:Traxoprodil (CP-101606) 10513:Epipregnanolone sulfate 9123:Nicotinic acetylcholine 8665:Trends in Neurosciences 7748:10.1073/pnas.0914064107 6928:10.1073/pnas.86.23.9584 6196:Trends in Neurosciences 5725:Brain Research Bulletin 5396:Trends in Neurosciences 4057:10.1126/science.aay3302 3991:Bading H (March 2017). 3766:10.1602/neurorx.1.1.101 3157:Chinese Medical Journal 3130:Pharmacological Reviews 3039:10.1056/NEJMcibr0902052 2632:Research suggests that 2538:NMDAR antagonists like 2444:Therapeutic application 1626:noncompetitive blockers 1000:theta burst stimulation 915:GluN2B to GluN2C switch 856:GluN2B to GluN2A switch 514:The NMDA receptor is a 128:positively charged ions 12278:Molecular neuroscience 12173:Proton pump inhibitors 11892:Surface wave detection 11560:Allosteric modulators: 11495:Ipenoxazone (MLV-6976) 11150:Pethidine (meperidine) 10771:Licostinel (ACEA-1021) 10693:Apimostinel (NRX-1074) 10357:Apimostinel (NRX-1074) 10325:Glycine site agonists: 10157:Licostinel (ACEA-1021) 9868:Licostinel (ACEA-1021) 9753:Mibampator (LY-451395) 8409:(Suppl 5): S497–S502. 8338:. Scientific American. 7675:Toxicological Sciences 7133:Clinical trial number 6384:10.1124/mol.104.005983 6372:Molecular Pharmacology 6254:10.1124/mol.104.008185 6242:Molecular Pharmacology 5374:Henchcliffe C (2007). 3858:10.1038/sj.bjp.0706444 2892:Physiological Research 2749:traumatic brain injury 2485:long-term potentiation 2358: 2319: 2299: 2072: 1650:7-Chlorokynurenic acid 1645:7-chlorokynurenic acid 1574: 1419: 1377: 1321:Dehydroepiandrosterone 1089: 1078: 1051:temporal lobe epilepsy 1018:temporal lobe epilepsy 924:Role in excitotoxicity 865: 769: 625:agonist-binding module 554: 539:for memantine, Mg and 511: 422: 351:neurological disorders 271:(nNOS) expression and 94:, the other two being 53: 11708:Anti-Hebbian learning 11229:CO-101244 (PD-174494) 10945:Delucemine (NPS-1506) 10895:Alazocine (SKF-10047) 8830:cell surface receptor 8790:- The Interactive Fly 8463:10.1038/sj.mp.4001648 8278:Wijesinghe R (2014). 7855:10.1101/lm.031351.113 7843:Learning & Memory 7687:10.1093/toxsci/kfq111 7071:10.1038/sj.mp.4000976 6786:10.1007/s007260070047 5963:Nature Communications 4785:10.1093/cercor/bht354 4687:10.1093/cercor/bhx357 3842:"The glutamate story" 3288:10.1089/ars.2012.5100 2898:(Suppl 1): S191–203. 2694:. These are known as 2534:Clinical significance 2353: 2314: 2294: 2083:25-Hydroxycholesterol 2063: 2004:– an opioid analgesic 1998:– an opioid analgesic 1779:Eupenicillium shearii 1569: 1407: 1372: 1084: 1069: 983:transcription factors 863: 767: 664:x-ray crystallography 549: 510:NR1/NR2 NMDA receptor 506: 420: 269:nitric oxide synthase 212:effects of the drugs 149:The NMDA receptor is 82:and predominantly Ca 36: 28:NDMA (disambiguation) 12128:Integrase inhibitors 12103:Direct Xa inhibitors 11785:Bernhard Hassenstein 11718:Ultrasound avoidance 11693:Fixed action pattern 11656:Coincidence detector 11249:Radiprodil (RGH-896) 11224:Buphenine (nylidrin) 10801:Rapastinel (GLYX-13) 10616:Midafotel (d-CPPene) 10523:Pregnenolone sulfate 10447:Rapastinel (GLYX-13) 10238:Pregnenolone sulfate 9979:Pregnenolone sulfate 9495:Purinergic receptors 8770:at Wikimedia Commons 8450:Molecular Psychiatry 8358:Molecular Psychiatry 7112:10.1093/brain/awh354 7058:Molecular Psychiatry 4357:(Suppl 1): S23–S32. 4009:10.1084/jem.20161673 2649:, in turn affecting 2481:coincidence detector 1339:Pregnenolone sulfate 828:postsynaptic density 655:protein phosphatases 11852:Animal echolocation 11790:Werner E. Reichardt 11740:Walter Heiligenberg 10480:-Hydroxycholesterol 10291:Homoquinolinic acid 10264:Main site agonists: 10022:Main site agonists: 9616:5-Fluorowillardiine 9613:Main site agonists: 8297:10.9740/mhc.n207179 8241:1984Natur.307..462N 8077:2015NatSR...514781T 7900:1990Natur.345..347T 7798:2000Sci...290.2155H 7792:(5499): 2155–2159. 7739:2010PNAS..10722278F 7733:(51): 22278–22283. 7391:Nature Neuroscience 7021:10.1038/nature10180 6919:1989PNAS...86.9584F 6532:10.1093/ijnp/pyy101 5975:2020NatCo..11.4966B 5498:(48): 18880–18892. 5449:(33): 11246–11250. 5126:(38): 10165–10175. 4938:2000SciAm.282d..62T 4926:Scientific American 4834:2015PLSCB..11E4559B 4724:Nature Neuroscience 4453:2010PLoSO...513342T 3896:Nature Neuroscience 3543:Nature Neuroscience 3337:2014PLoSO...998079C 3084:1991Natur.354...31M 2992:10.1038/nature04089 2984:2005Natur.438..185F 2743:in situations like 2564:general anesthetics 2489:synaptic plasticity 2460:Receptor modulation 2336:Alzheimer's disease 2216:synaptic plasticity 2137:synaptic plasticity 1513:Homoquinolinic acid 755:GluN1-4a, GluN1-4b; 752:GluN1-3a, GluN1-3b; 749:GluN1-2a, GluN1-2b; 670:Mechanism of action 398:medicinal chemistry 324:has this property. 170:glutamate receptors 136:synaptic plasticity 70:(also known as the 12198:Tubulin inhibitors 11815:Fernando Nottebohm 11713:Sound localization 11688:Lateral inhibition 10828:Diethylenetriamine 10507:prasterone sulfate 10282:Homocysteic acid ( 10025:5-Bromowillardiine 9263:β1δε - Muscle type 8842:Cys-loop receptors 8610:10.1038/nm0706-780 8370:10.1038/mp.2009.80 8065:Scientific Reports 7145:ClinicalTrials.gov 5823:The Neuroscientist 4406:10.1042/BST0340877 4051:(6513): eaay3302. 2611:4-chlorokynurenine 2588:recreational drugs 2474:signaling pathways 2359: 2320: 2300: 2153:Src family kinases 2073: 1928:Dextropropoxyphene 1641:4-Chlorokynurenine 1583:recreational drugs 1575: 1460:epileptic seizures 1420: 1378: 1090: 1079: 866: 770: 647:cytoplasmic domain 629:potassium channels 555: 512: 423: 267:via inhibition of 224:concentrations of 178:reversal potential 176:, with a combined 80:glutamate receptor 54: 12245: 12244: 12193:TRPV1 antagonists 12133:Lipase inhibitors 11949: 11948: 11836:Slice preparation 11698:Krogh's Principle 11673:Feature detection 11603: 11602: 11454: 11410:Trichloroethylene 11355:Ethanol (alcohol) 10720: 10663:4-Cl-KYN (AV-101) 10431: 10423: 10390: 10382: 10374: 10331: 10316:Tetrazolylglycine 10285: 10223:Ethanol (alcohol) 10212:sodium thiopental 10030:5-Iodowillardiine 9939:Ethanol (alcohol) 9923:sodium thiopental 9552: 9551: 9548: 9547: 9476: 9475: 9307:Ligand-gated only 9289: 9288: 8766:Media related to 8235:(5950): 462–465. 8209:978-0-87893-697-7 8159:(27): 6171–6180. 8129:978-0-87893-697-7 8085:10.1038/srep14781 7995:978-1-4200-4414-0 7894:(6273): 347–350. 7540:(5300): 674–678. 7495:(36): 8209–8216. 7105:(Pt 2): 300–307. 7015:(7355): 249–253. 6913:(23): 9584–9587. 6874:(13): 1347–1360. 6335:Neuropharmacology 5686:(18): 6627–6638. 5547:(29): 9330–9343. 5175:(10): 2301–2312. 5028:(11): 2956–2963. 4979:(11): 2846–2857. 4887:(40): 8885–8895. 4591:10.1002/jnr.23347 4546:(14): 2603–2617. 4400:(Pt 5): 877–881. 4335:978-1-60913-345-0 4317:Maher TJ (2013). 4286:10.1021/cn300180a 4150:Neuropharmacology 4113:10.1021/cr100264t 3852:(S1): S100–S108. 3549:(11): 1039–1042. 3282:(15): 1766–1782. 2978:(7065): 185–192. 2651:neural plasticity 2526:processes (e.g., 1613:(a metabolite of 1525: 1495: 1449: 1443: 1438: 1429: 1415: 1293: 1286: 1258: 1251: 1208:Tetrazolylglycine 1197: 1193: 1183: 1176: 1132:-NMDA receptors. 1127: 1123: 1113: 1072: 1038:neurodegenerative 989:Neural plasticity 561: 339: 165: 118: 100:kainate receptors 64: 12290: 12237:Renin inhibitors 12083:c-Met inhibitors 12007:Drug development 11976: 11969: 11962: 11953: 11952: 11937: 11936: 11925: 11924: 11902:Mechanoreception 11897:Electroreception 11810:Masakazu Konishi 11775:Jörg-Peter Ewert 11630: 11623: 11616: 11607: 11606: 11452: 11405:Trichloroethanol 10965:Dextromethorphan 10718: 10502: 10491: 10487: 10429: 10421: 10388: 10380: 10372: 10329: 10283: 10254: 10250: 10012: 10008: 9843:Fanapanel (MPQX) 9603: 9599: 9579: 9572: 9565: 9556: 9555: 9491: 9490: 9303: 9302: 8847: 8846: 8819: 8812: 8805: 8796: 8795: 8765: 8750: 8749: 8739: 8729: 8705: 8699: 8698: 8688: 8656: 8650: 8641: 8635: 8629: 8623: 8622: 8612: 8588: 8582: 8581: 8545: 8536: 8535: 8529: 8521: 8519: 8518: 8482: 8476: 8475: 8465: 8441: 8435: 8434: 8398: 8392: 8391: 8381: 8349: 8340: 8339: 8331: 8325: 8324: 8316: 8310: 8309: 8299: 8284:Ment Health Clin 8275: 8269: 8268: 8249:10.1038/307462a0 8224: 8218: 8217: 8212:. Archived from 8193: 8187: 8186: 8176: 8144: 8138: 8137: 8132:. Archived from 8113: 8107: 8106: 8096: 8056: 8050: 8049: 8021: 8008: 8007: 7977: 7971: 7970: 7945:(3): 1257–1263. 7934: 7928: 7927: 7908:10.1038/345347a0 7883: 7877: 7876: 7866: 7834: 7828: 7827: 7817: 7777: 7771: 7770: 7760: 7750: 7718: 7709: 7708: 7698: 7666: 7660: 7659: 7634:(4): 1652–1660. 7623: 7617: 7616: 7606: 7596: 7572: 7566: 7565: 7529: 7523: 7522: 7512: 7480: 7474: 7473: 7463: 7431: 7425: 7424: 7414: 7382: 7376: 7375: 7347: 7341: 7340: 7315:(4): 1516–1521. 7303: 7297: 7296: 7260: 7247: 7246: 7236: 7226: 7202: 7196: 7195: 7185: 7153: 7147: 7139:for "Effects of 7131: 7125: 7124: 7114: 7090: 7084: 7083: 7073: 7049: 7043: 7042: 7032: 7000: 6994: 6993: 6957: 6951: 6950: 6940: 6930: 6898: 6892: 6891: 6863: 6857: 6856: 6846: 6836: 6812: 6806: 6805: 6768: 6762: 6761: 6724: 6718: 6717: 6707: 6683: 6677: 6676: 6640: 6631: 6630: 6612: 6588: 6579: 6578: 6576: 6575: 6560: 6554: 6553: 6543: 6511: 6505: 6495: 6489: 6488: 6478: 6461:(8): 2005–2013. 6446: 6440: 6439: 6410: 6404: 6403: 6378:(5): 1648–1654. 6367: 6361: 6360: 6350: 6326: 6317: 6316: 6280: 6274: 6273: 6248:(5): 1470–1484. 6236: 6230: 6229: 6219: 6187: 6181: 6180: 6162: 6138: 6132: 6131: 6103: 6097: 6096: 6086: 6076: 6052: 6046: 6045: 6035: 6011: 6005: 6004: 5994: 5954: 5941: 5940: 5912: 5906: 5905: 5895: 5863: 5857: 5856: 5846: 5814: 5808: 5807: 5797: 5787: 5763: 5757: 5756: 5720: 5714: 5713: 5703: 5671: 5665: 5664: 5654: 5622: 5616: 5615: 5605: 5596:(5): 1119–1133. 5581: 5575: 5574: 5564: 5532: 5526: 5525: 5515: 5483: 5477: 5476: 5466: 5434: 5428: 5427: 5391: 5380: 5379: 5371: 5365: 5364: 5354: 5322: 5316: 5315: 5305: 5281: 5252: 5251: 5241: 5224:(8): 2404–2413. 5209: 5203: 5202: 5192: 5160: 5154: 5153: 5143: 5111: 5105: 5104: 5086: 5062: 5056: 5055: 5045: 5013: 5007: 5006: 4996: 4964: 4958: 4957: 4921: 4915: 4914: 4904: 4872: 4866: 4865: 4855: 4845: 4828:(12): e1004559. 4813: 4807: 4806: 4796: 4779:(6): 1596–1607. 4764: 4758: 4757: 4747: 4730:(9): 1251–1259. 4715: 4709: 4708: 4698: 4681:(4): 1458–1471. 4666: 4660: 4659: 4649: 4617: 4611: 4610: 4570: 4564: 4563: 4534: 4528: 4527: 4491: 4485: 4484: 4474: 4464: 4432: 4426: 4425: 4389: 4383: 4382: 4346: 4340: 4339: 4323: 4314: 4308: 4307: 4297: 4265: 4252: 4251: 4223: 4214: 4213: 4185: 4176: 4175: 4165: 4141: 4135: 4134: 4124: 4107:(5): 3516–3604. 4101:Chemical Reviews 4092: 4077: 4076: 4040: 4031: 4030: 4020: 3988: 3982: 3981: 3971: 3939: 3928: 3927: 3891: 3880: 3879: 3869: 3837: 3831: 3830: 3794: 3788: 3787: 3777: 3745: 3726: 3725: 3689: 3683: 3682: 3654: 3641: 3640: 3604: 3575: 3574: 3538: 3523: 3522: 3504: 3495:(6): 1611–1626. 3480: 3459: 3458: 3448: 3424: 3411: 3410: 3382: 3369: 3368: 3358: 3348: 3316: 3310: 3309: 3299: 3267: 3261: 3260: 3234: 3225: 3216: 3215: 3179: 3173: 3172: 3152: 3146: 3145: 3121: 3112: 3111: 3092:10.1038/354031a0 3067: 3061: 3060: 3050: 3018: 3012: 3011: 2967: 2958: 2957: 2956: 2955: 2932: 2926: 2925: 2907: 2883: 2877: 2876: 2866: 2834: 2825: 2824: 2811: 2787: 2648: 2644: 2597:(JNJ-54135419), 2568:dextromethorphan 2470:second messenger 2263:, agitation and 2206:Proteins of the 2094:Conus geographus 1932:opioid analgesic 1924: 1920: 1904:antiparkinsonian 1711:Dextromethorphan 1615:dextromethorphan 1523: 1493: 1447: 1441: 1436: 1427: 1413: 1400:Partial agonists 1291: 1284: 1256: 1249: 1225:Amanita muscaria 1214:Homocysteic acid 1195: 1191: 1181: 1174: 1149:Hebbian learning 1125: 1121: 1111: 1070: 801:gene duplication 559: 337: 202:dextromethorphan 163: 116: 62: 12298: 12297: 12293: 12292: 12291: 12289: 12288: 12287: 12248: 12247: 12246: 12241: 12226: 12168:PDE5 inhibitors 12158:NS5A inhibitors 12143:mTOR inhibitors 12072: 12036: 12030: 11990:Steps in design 11985: 11980: 11950: 11945: 11913: 11867:Vision in toads 11840: 11819: 11770:Erich von Holst 11765:Karl von Frisch 11723: 11639: 11634: 11604: 11599: 11567: 11465:Flufenamic acid 11400:Trichloroethane 11175:Rhynchophylline 11095:Methoxphenidine 11060:Levomilnacipran 10960:Dextromethadone 10885:α-Endopsychosin 10489: 10401:Dimethylglycine 10311:Quinolinic acid 10252: 10242: 10080:Quisqualic acid 10010: 10000: 9656:Quisqualic acid 9601: 9591: 9583: 9553: 9544: 9472: 9466: 9458: 9436: 9371: 9285: 9267: 9262: 9254:- Ganglion type 9253: 9249: 9241: 9233: 9229: 9221: 9217: 9117: 9108: 9100: 9092: 9084: 9067: 9061: 9053: 9045: 9036: 9006: 8998: 8990: 8982: 8974: 8966: 8958: 8950: 8942: 8934: 8926: 8918: 8910: 8893: 8862: 8836: 8823: 8788:NMDA receptor 1 8758: 8753: 8706: 8702: 8657: 8653: 8647:, available at 8642: 8638: 8630: 8626: 8597:Nature Medicine 8589: 8585: 8546: 8539: 8523: 8522: 8516: 8514: 8483: 8479: 8442: 8438: 8399: 8395: 8350: 8343: 8334:Stix G (2014). 8332: 8328: 8319:Poon L (2014). 8317: 8313: 8276: 8272: 8225: 8221: 8210: 8194: 8190: 8145: 8141: 8130: 8114: 8110: 8057: 8053: 8022: 8011: 7996: 7978: 7974: 7935: 7931: 7884: 7880: 7835: 7831: 7778: 7774: 7719: 7712: 7667: 7663: 7624: 7620: 7573: 7569: 7530: 7526: 7481: 7477: 7432: 7428: 7383: 7379: 7348: 7344: 7304: 7300: 7277:10.1038/nrn2229 7271:(10): 803–808. 7261: 7250: 7203: 7199: 7154: 7150: 7132: 7128: 7091: 7087: 7050: 7046: 7001: 6997: 6958: 6954: 6899: 6895: 6864: 6860: 6813: 6809: 6769: 6765: 6725: 6721: 6684: 6680: 6657:10.1038/nrd3793 6641: 6634: 6610:10.1038/nrd4178 6589: 6582: 6573: 6571: 6561: 6557: 6512: 6508: 6496: 6492: 6447: 6443: 6411: 6407: 6368: 6364: 6327: 6320: 6281: 6277: 6237: 6233: 6188: 6184: 6139: 6135: 6104: 6100: 6053: 6049: 6012: 6008: 5955: 5944: 5913: 5909: 5864: 5860: 5815: 5811: 5764: 5760: 5721: 5717: 5672: 5668: 5623: 5619: 5582: 5578: 5533: 5529: 5484: 5480: 5435: 5431: 5392: 5383: 5372: 5368: 5323: 5319: 5282: 5255: 5210: 5206: 5161: 5157: 5112: 5108: 5063: 5059: 5014: 5010: 4965: 4961: 4922: 4918: 4873: 4869: 4814: 4810: 4773:Cerebral Cortex 4765: 4761: 4716: 4712: 4675:Cerebral Cortex 4667: 4663: 4618: 4614: 4571: 4567: 4535: 4531: 4508:10.1038/nrn2717 4502:(10): 701–712. 4492: 4488: 4433: 4429: 4390: 4386: 4363:10.1002/gps.938 4347: 4343: 4336: 4321: 4315: 4311: 4266: 4255: 4224: 4217: 4186: 4179: 4142: 4138: 4093: 4080: 4041: 4034: 3989: 3985: 3960:10.1038/nrn2911 3954:(10): 682–696. 3940: 3931: 3892: 3883: 3838: 3834: 3795: 3791: 3746: 3729: 3690: 3686: 3655: 3644: 3621:10.1038/nrd1958 3605: 3578: 3539: 3526: 3481: 3462: 3425: 3414: 3383: 3372: 3317: 3313: 3268: 3264: 3232: 3226: 3219: 3180: 3176: 3163:(10): 948–956. 3153: 3149: 3122: 3115: 3078:(6348): 31–37. 3068: 3064: 3019: 3015: 2968: 2961: 2953: 2951: 2933: 2929: 2884: 2880: 2835: 2828: 2788: 2781: 2777: 2765: 2753:clinical trials 2745:ischemic stroke 2710:methamphetamine 2646: 2536: 2462: 2446: 2439: 2435: 2431: 2427: 2418: 2411: 2406: 2401: 2396: 2382: 2375: 2369: 2362:effectiveness: 2348: 2329:anticholinergic 2309: 2289: 2273: 2256: 2123:Aminoglycosides 2108: 2103: 2070: 2043: 2029: 1922: 1832: 1634: 1599:Olney's lesions 1564: 1558: 1479: 1456:ischemic stroke 1402: 1394:clinical trials 1367: 1231:Quinolinic acid 1157: 1118:serine racemase 1064: 1059: 1034: 1009: 996:NMDA antagonist 991: 964:protein signals 955: 926: 917: 858: 762: 732: 727: 676:neuroplasticity 672: 651:protein kinases 636:membrane domain 501: 415: 379:neuroprotection 330: 317:neuroprotection 284: 261:methamphetamine 248: 39:allosteric site 31: 24: 17: 12: 11: 5: 12296: 12286: 12285: 12280: 12275: 12270: 12265: 12260: 12258:Cell signaling 12243: 12242: 12240: 12239: 12234: 12229: 12224: 12220: 12215: 12210: 12205: 12200: 12195: 12190: 12185: 12180: 12175: 12170: 12165: 12160: 12155: 12150: 12145: 12140: 12135: 12130: 12125: 12120: 12115: 12110: 12105: 12100: 12095: 12090: 12085: 12080: 12078:Cephalosporins 12075: 12070: 12066: 12061: 12056: 12051: 12049:ACE inhibitors 12046: 12040: 12038: 12032: 12031: 12029: 12028: 12027: 12026: 12025: 12024: 12014: 12004: 11999: 11997:Drug discovery 11993: 11991: 11987: 11986: 11979: 11978: 11971: 11964: 11956: 11947: 11946: 11944: 11943: 11931: 11918: 11915: 11914: 11912: 11911: 11910: 11909: 11899: 11894: 11889: 11887:Vocal learning 11884: 11879: 11874: 11869: 11864: 11859: 11854: 11848: 11846: 11842: 11841: 11839: 11838: 11833: 11827: 11825: 11821: 11820: 11818: 11817: 11812: 11807: 11802: 11797: 11792: 11787: 11782: 11777: 11772: 11767: 11762: 11760:Donald Kennedy 11757: 11755:Donald Griffin 11752: 11747: 11745:Niko Tinbergen 11742: 11737: 11731: 11729: 11725: 11724: 11722: 11721: 11715: 11710: 11705: 11703:Hebbian theory 11700: 11695: 11690: 11685: 11680: 11675: 11670: 11665: 11658: 11653: 11647: 11645: 11641: 11640: 11633: 11632: 11625: 11618: 11610: 11601: 11600: 11598: 11597: 11590: 11583: 11572: 11569: 11568: 11566: 11565: 11553: 11552: 11542: 11537: 11532: 11527: 11522: 11517: 11512: 11507: 11502: 11497: 11492: 11487: 11482: 11477: 11472: 11467: 11462: 11457: 11449: 11444: 11439: 11434: 11422: 11417: 11412: 11407: 11402: 11397: 11392: 11387: 11382: 11377: 11375:Methoxyflurane 11372: 11367: 11362: 11357: 11352: 11347: 11342: 11337: 11332: 11327: 11322: 11310: 11305: 11293: 11288: 11283: 11271: 11266: 11261: 11256: 11251: 11246: 11241: 11236: 11231: 11226: 11221: 11216: 11207: 11202: 11197: 11192: 11187: 11182: 11177: 11172: 11167: 11162: 11157: 11152: 11147: 11142: 11137: 11132: 11127: 11122: 11120:Nitromemantine 11117: 11112: 11107: 11102: 11097: 11092: 11087: 11082: 11077: 11072: 11067: 11062: 11057: 11055:Levomethorphan 11052: 11047: 11042: 11037: 11032: 11027: 11022: 11017: 11012: 11007: 11002: 10997: 10992: 10987: 10982: 10977: 10975:Dieticyclidine 10972: 10967: 10962: 10957: 10955:Dextrallorphan 10952: 10947: 10942: 10937: 10932: 10927: 10922: 10917: 10912: 10910:Argiotoxin-636 10907: 10902: 10897: 10892: 10887: 10882: 10877: 10872: 10867: 10862: 10857: 10852: 10847: 10835: 10830: 10825: 10823:Diaminopropane 10820: 10815: 10803: 10798: 10793: 10788: 10783: 10778: 10773: 10768: 10763: 10758: 10753: 10751:Kynurenic acid 10748: 10743: 10738: 10733: 10728: 10723: 10715: 10710: 10705: 10700: 10695: 10690: 10685: 10680: 10675: 10670: 10665: 10653: 10648: 10643: 10638: 10633: 10628: 10623: 10618: 10613: 10608: 10603: 10598: 10593: 10588: 10583: 10578: 10573: 10568: 10563: 10558: 10553: 10541: 10540: 10535: 10530: 10525: 10520: 10515: 10510: 10497: 10482: 10466: 10461: 10449: 10444: 10439: 10434: 10426: 10418: 10413: 10408: 10403: 10398: 10393: 10385: 10377: 10369: 10364: 10359: 10354: 10349: 10344: 10339: 10334: 10318: 10313: 10308: 10303: 10298: 10293: 10288: 10279: 10274: 10269: 10257: 10255: 10244: 10243: 10241: 10240: 10235: 10230: 10225: 10220: 10215: 10194: 10189: 10184: 10179: 10174: 10169: 10164: 10159: 10154: 10152:Kynurenic acid 10149: 10144: 10139: 10134: 10129: 10124: 10115: 10114: 10109: 10104: 10099: 10094: 10082: 10077: 10072: 10067: 10062: 10057: 10052: 10047: 10042: 10037: 10032: 10027: 10015: 10013: 10002: 10001: 9999: 9998: 9986: 9981: 9976: 9971: 9966: 9961: 9956: 9951: 9946: 9941: 9936: 9931: 9926: 9905: 9900: 9895: 9890: 9885: 9880: 9875: 9870: 9865: 9860: 9858:Kynurenic acid 9855: 9850: 9845: 9840: 9835: 9830: 9825: 9820: 9815: 9810: 9801: 9800: 9795: 9790: 9785: 9780: 9775: 9770: 9765: 9760: 9755: 9750: 9745: 9740: 9735: 9730: 9725: 9720: 9715: 9710: 9705: 9700: 9695: 9690: 9685: 9680: 9675: 9670: 9658: 9653: 9648: 9643: 9638: 9633: 9628: 9623: 9618: 9606: 9604: 9593: 9592: 9582: 9581: 9574: 9567: 9559: 9550: 9549: 9546: 9545: 9543: 9542: 9541: 9540: 9535: 9530: 9525: 9520: 9515: 9510: 9499: 9497: 9488: 9486:gated channels 9478: 9477: 9474: 9473: 9471: 9470: 9469: 9468: 9464: 9460: 9456: 9446: 9444: 9438: 9437: 9435: 9434: 9433: 9432: 9427: 9422: 9417: 9412: 9407: 9402: 9397: 9392: 9381: 9379: 9373: 9372: 9370: 9369: 9368: 9367: 9362: 9357: 9352: 9347: 9337: 9331: 9326: 9321: 9311: 9309: 9300: 9291: 9290: 9287: 9286: 9284: 9283: 9281:Zinc-activated 9277: 9275: 9269: 9268: 9266: 9265: 9260: 9256: 9251: 9247: 9243: 9239: 9235: 9231: 9227: 9223: 9219: 9215: 9207: 9206: 9201: 9196: 9191: 9186: 9181: 9176: 9171: 9166: 9161: 9156: 9151: 9146: 9141: 9136: 9127: 9125: 9119: 9118: 9116: 9115: 9110: 9106: 9102: 9098: 9094: 9090: 9086: 9082: 9077: 9075: 9069: 9068: 9066: 9065: 9064: 9063: 9059: 9055: 9051: 9047: 9043: 9034: 9030: 9029: 9028: 9023: 9018: 9013: 9008: 9004: 9000: 8996: 8992: 8988: 8984: 8980: 8976: 8972: 8968: 8964: 8960: 8956: 8952: 8948: 8944: 8940: 8936: 8932: 8928: 8924: 8920: 8916: 8908: 8903: 8901: 8895: 8894: 8892: 8891: 8890: 8889: 8884: 8879: 8874: 8869: 8860: 8855: 8853: 8851:5-HT/serotonin 8844: 8838: 8837: 8822: 8821: 8814: 8807: 8799: 8793: 8792: 8781: 8776: 8771: 8757: 8756:External links 8754: 8752: 8751: 8700: 8671:(5): 234–242. 8651: 8636: 8624: 8603:(7): 780–784. 8583: 8537: 8477: 8456:(6): 525–537. 8436: 8393: 8364:(3): 237–249. 8341: 8326: 8311: 8270: 8219: 8216:on 2011-09-27. 8208: 8188: 8139: 8136:on 2011-09-27. 8128: 8108: 8051: 8009: 7994: 7972: 7929: 7878: 7849:(9): 505–517. 7829: 7772: 7710: 7681:(1): 249–263. 7661: 7618: 7567: 7524: 7475: 7446:(2): 415–424. 7426: 7403:10.1038/nn1914 7397:(7): 880–886. 7377: 7358:(4): 381–388. 7342: 7298: 7248: 7217:(5): 702–713. 7197: 7168:(2): 283–291. 7148: 7126: 7085: 7064:(4): 359–367. 7044: 6995: 6968:(1–2): 79–85. 6962:Brain Research 6952: 6893: 6858: 6807: 6780:(1): 177–179. 6763: 6730:Brain Research 6719: 6698:(5): 187–193. 6678: 6632: 6580: 6555: 6526:(3): 247–259. 6506: 6490: 6441: 6422:(3): 261–270. 6405: 6362: 6318: 6285:Science's STKE 6275: 6231: 6202:(2): 103–114. 6182: 6153:(2): 178–190. 6133: 6114:(2): 193–201. 6098: 6047: 6026:(2): 589–594. 6006: 5942: 5923:(5): 266–275. 5907: 5858: 5809: 5778:(3): 633–646. 5758: 5715: 5666: 5637:(3): 496–508. 5617: 5576: 5527: 5478: 5429: 5381: 5366: 5337:(1): 185–196. 5317: 5296:(2): 279–293. 5253: 5204: 5155: 5106: 5077:(2): 279–289. 5057: 5008: 4959: 4916: 4867: 4808: 4759: 4710: 4661: 4632:(4): 736–749. 4612: 4585:(6): 679–691. 4565: 4529: 4486: 4447:(10): e13342. 4427: 4384: 4341: 4334: 4309: 4280:(2): 255–260. 4253: 4215: 4177: 4136: 4078: 4032: 4003:(3): 569–578. 3983: 3929: 3902:(5): 405–414. 3881: 3832: 3805:(3): 279–298. 3789: 3760:(1): 101–110. 3727: 3700:(3): 807–819. 3684: 3665:(3): 253–259. 3642: 3615:(2): 160–170. 3576: 3524: 3460: 3439:(4): 415–423. 3412: 3370: 3311: 3262: 3217: 3190:(3): 327–335. 3174: 3147: 3113: 3062: 3033:(3): 302–303. 3013: 2959: 2927: 2878: 2849:(2): 581–589. 2826: 2802:(3): 493–503. 2778: 2776: 2773: 2772: 2771: 2764: 2761: 2737:excitotoxicity 2655:AMPA receptors 2619:mood disorders 2613:(AV-101), and 2609:(AGN-241751), 2580:hallucinogenic 2535: 2532: 2528:excitotoxicity 2461: 2458: 2445: 2442: 2437: 2433: 2429: 2425: 2417: 2414: 2409: 2404: 2399: 2394: 2385: 2384: 2380: 2379:Two methyl (CH 2377: 2373: 2370: 2367: 2347: 2344: 2308: 2305: 2288: 2285: 2272: 2269: 2261:hallucinations 2255: 2252: 2251: 2250: 2234: 2227: 2204: 2198: 2188: 2174: 2168: 2146: 2140: 2126: 2107: 2104: 2102: 2099: 2098: 2097: 2086: 2068: 2050:Nitromemantine 2048:could result. 2041: 2028: 2027:Nitromemantine 2025: 2024: 2023: 2014: 2005: 1999: 1993: 1979: 1974:and potential 1965: 1956: 1934: 1925: 1916:used to treat 1907: 1889: 1888: 1882: 1876: 1870: 1864: 1858: 1852: 1846: 1840: 1834: 1830: 1824: 1818: 1812: 1806: 1800: 1794: 1791:Kynurenic acid 1788: 1782: 1771: 1765: 1759: 1753: 1747: 1741: 1735: 1729: 1723: 1717: 1708: 1706:argiotoxin-636 1699: 1689: 1683: 1677: 1671: 1662:Argiotoxin-636 1659: 1653: 1647: 1633: 1630: 1587:hallucinogenic 1560:Main article: 1557: 1554: 1553: 1552: 1546: 1540: 1530: 1529: 1526:-aspartic acid 1516: 1510: 1504: 1486: 1478: 1475: 1469:(GLYX-13) and 1444:-phenylalanine 1430:-aspartic acid 1416:-aspartic acid 1401: 1398: 1366: 1363: 1362: 1361: 1360: 1359: 1353: 1344: 1343: 1342: 1336: 1330: 1324: 1318: 1312: 1301: 1300: 1299: 1298: 1297: 1277: 1271: 1262: 1236: 1235: 1234: 1228: 1217: 1211: 1199: 1184:-aspartic acid 1177:-aspartic acid 1156: 1153: 1063: 1060: 1058: 1055: 1043:polymicrogyria 1033: 1030: 1008: 1005: 990: 987: 954: 951: 930:excitotoxicity 925: 922: 916: 913: 896: 895: 892: 889: 857: 854: 832:working memory 817:pyramidal cell 815:. However, in 761: 758: 757: 756: 753: 750: 747: 731: 728: 726: 723: 671: 668: 659: 658: 643: 632: 621: 590:heterotetramer 570:depolarization 533:nervous system 500: 497: 496: 495: 494: 493: 487: 478: 477: 476: 470: 464: 458: 449: 414: 411: 329: 326: 304:excitotoxicity 291:. Since 1989, 282: 251:, which leads 246: 188:drugs such as 138:and mediating 15: 9: 6: 4: 3: 2: 12295: 12284: 12281: 12279: 12276: 12274: 12271: 12269: 12266: 12264: 12261: 12259: 12256: 12255: 12253: 12238: 12235: 12233: 12230: 12228: 12221: 12219: 12216: 12214: 12211: 12209: 12206: 12204: 12201: 12199: 12196: 12194: 12191: 12189: 12186: 12184: 12181: 12179: 12176: 12174: 12171: 12169: 12166: 12164: 12161: 12159: 12156: 12154: 12151: 12149: 12146: 12144: 12141: 12139: 12136: 12134: 12131: 12129: 12126: 12124: 12121: 12119: 12116: 12114: 12111: 12109: 12106: 12104: 12101: 12099: 12096: 12094: 12091: 12089: 12086: 12084: 12081: 12079: 12076: 12074: 12067: 12065: 12064:Beta-blockers 12062: 12060: 12059:Antiandrogens 12057: 12055: 12052: 12050: 12047: 12045: 12042: 12041: 12039: 12033: 12023: 12020: 12019: 12018: 12015: 12013: 12010: 12009: 12008: 12005: 12003: 12000: 11998: 11995: 11994: 11992: 11988: 11984: 11977: 11972: 11970: 11965: 11963: 11958: 11957: 11954: 11942: 11941: 11932: 11930: 11929: 11920: 11919: 11916: 11908: 11905: 11904: 11903: 11900: 11898: 11895: 11893: 11890: 11888: 11885: 11883: 11880: 11878: 11875: 11873: 11870: 11868: 11865: 11863: 11860: 11858: 11855: 11853: 11850: 11849: 11847: 11843: 11837: 11834: 11832: 11829: 11828: 11826: 11822: 11816: 11813: 11811: 11808: 11806: 11803: 11801: 11798: 11796: 11793: 11791: 11788: 11786: 11783: 11781: 11778: 11776: 11773: 11771: 11768: 11766: 11763: 11761: 11758: 11756: 11753: 11751: 11750:Konrad Lorenz 11748: 11746: 11743: 11741: 11738: 11736: 11733: 11732: 11730: 11726: 11719: 11716: 11714: 11711: 11709: 11706: 11704: 11701: 11699: 11696: 11694: 11691: 11689: 11686: 11684: 11683:NMDA receptor 11681: 11679: 11676: 11674: 11671: 11669: 11666: 11664: 11663: 11659: 11657: 11654: 11652: 11649: 11648: 11646: 11642: 11638: 11637:Neuroethology 11631: 11626: 11624: 11619: 11617: 11612: 11611: 11608: 11596: 11595: 11591: 11589: 11588: 11584: 11582: 11581: 11578: 11574: 11573: 11570: 11564: 11561: 11558: 11555: 11554: 11550: 11546: 11545:Transcrocetin 11543: 11541: 11540:Psychotridine 11538: 11536: 11533: 11531: 11528: 11526: 11523: 11521: 11520:Niflumic acid 11518: 11516: 11513: 11511: 11508: 11506: 11503: 11501: 11498: 11496: 11493: 11491: 11488: 11486: 11483: 11481: 11478: 11476: 11473: 11471: 11468: 11466: 11463: 11461: 11458: 11456: 11450: 11448: 11445: 11443: 11440: 11438: 11435: 11433: 11430: 11426: 11423: 11421: 11418: 11416: 11413: 11411: 11408: 11406: 11403: 11401: 11398: 11396: 11393: 11391: 11388: 11386: 11383: 11381: 11380:Nitrous oxide 11378: 11376: 11373: 11371: 11368: 11366: 11363: 11361: 11358: 11356: 11353: 11351: 11348: 11346: 11345:Diethyl ether 11343: 11341: 11338: 11336: 11333: 11331: 11328: 11326: 11323: 11321: 11318: 11314: 11311: 11309: 11306: 11304: 11301: 11297: 11294: 11292: 11289: 11287: 11284: 11282: 11279: 11275: 11272: 11270: 11267: 11265: 11262: 11260: 11257: 11255: 11252: 11250: 11247: 11245: 11242: 11240: 11237: 11235: 11232: 11230: 11227: 11225: 11222: 11220: 11217: 11215: 11211: 11208: 11206: 11203: 11201: 11200:Tenocyclidine 11198: 11196: 11195:Tabernanthine 11193: 11191: 11188: 11186: 11185:Rolicyclidine 11183: 11181: 11178: 11176: 11173: 11171: 11168: 11166: 11163: 11161: 11160:Phencyclidine 11158: 11156: 11155:Phencyclamine 11153: 11151: 11148: 11146: 11143: 11141: 11138: 11136: 11133: 11131: 11128: 11126: 11123: 11121: 11118: 11116: 11113: 11111: 11108: 11106: 11103: 11101: 11098: 11096: 11093: 11091: 11090:Methoxetamine 11088: 11086: 11083: 11081: 11078: 11076: 11073: 11071: 11068: 11066: 11063: 11061: 11058: 11056: 11053: 11051: 11050:Levomethadone 11048: 11046: 11043: 11041: 11038: 11036: 11033: 11031: 11028: 11026: 11023: 11021: 11018: 11016: 11013: 11011: 11010:Fluorolintane 11008: 11006: 11003: 11001: 10998: 10996: 10993: 10991: 10988: 10986: 10983: 10981: 10978: 10976: 10973: 10971: 10968: 10966: 10963: 10961: 10958: 10956: 10953: 10951: 10948: 10946: 10943: 10941: 10938: 10936: 10933: 10931: 10928: 10926: 10923: 10921: 10918: 10916: 10913: 10911: 10908: 10906: 10903: 10901: 10898: 10896: 10893: 10891: 10888: 10886: 10883: 10881: 10878: 10876: 10873: 10871: 10868: 10866: 10863: 10861: 10858: 10856: 10853: 10851: 10848: 10846: 10843: 10839: 10836: 10834: 10831: 10829: 10826: 10824: 10821: 10819: 10816: 10814: 10811: 10807: 10804: 10802: 10799: 10797: 10794: 10792: 10789: 10787: 10784: 10782: 10779: 10777: 10774: 10772: 10769: 10767: 10764: 10762: 10759: 10757: 10754: 10752: 10749: 10747: 10744: 10742: 10739: 10737: 10734: 10732: 10729: 10727: 10724: 10722: 10716: 10714: 10711: 10709: 10706: 10704: 10701: 10699: 10696: 10694: 10691: 10689: 10686: 10684: 10681: 10679: 10676: 10674: 10671: 10669: 10666: 10664: 10661: 10657: 10654: 10652: 10649: 10647: 10644: 10642: 10639: 10637: 10634: 10632: 10629: 10627: 10624: 10622: 10619: 10617: 10614: 10612: 10609: 10607: 10604: 10602: 10599: 10597: 10594: 10592: 10591:Kaitocephalin 10589: 10587: 10584: 10582: 10579: 10577: 10574: 10572: 10569: 10567: 10564: 10562: 10559: 10557: 10554: 10552: 10549: 10546: 10543: 10542: 10539: 10536: 10534: 10531: 10529: 10526: 10524: 10521: 10519: 10516: 10514: 10511: 10508: 10504: 10498: 10495: 10488: 10483: 10481: 10479: 10474: 10470: 10467: 10465: 10462: 10460: 10457: 10453: 10450: 10448: 10445: 10443: 10440: 10438: 10435: 10433: 10427: 10425: 10419: 10417: 10414: 10412: 10409: 10407: 10404: 10402: 10399: 10397: 10394: 10392: 10386: 10384: 10378: 10376: 10370: 10368: 10365: 10363: 10360: 10358: 10355: 10353: 10350: 10348: 10345: 10343: 10340: 10338: 10335: 10333: 10326: 10322: 10319: 10317: 10314: 10312: 10309: 10307: 10304: 10302: 10299: 10297: 10296:Ibotenic acid 10294: 10292: 10289: 10287: 10280: 10278: 10275: 10273: 10270: 10268: 10265: 10262: 10259: 10258: 10256: 10251: 10245: 10239: 10236: 10234: 10231: 10229: 10226: 10224: 10221: 10219: 10216: 10213: 10209: 10208:pentobarbital 10205: 10202: 10198: 10195: 10193: 10190: 10188: 10185: 10183: 10180: 10178: 10175: 10173: 10170: 10168: 10165: 10163: 10160: 10158: 10155: 10153: 10150: 10148: 10147:Kaitocephalin 10145: 10143: 10140: 10138: 10135: 10133: 10130: 10128: 10125: 10123: 10120: 10117: 10116: 10113: 10110: 10108: 10105: 10103: 10100: 10098: 10095: 10093: 10092:Cyclothiazide 10090: 10086: 10083: 10081: 10078: 10076: 10073: 10071: 10068: 10066: 10063: 10061: 10060:Ibotenic acid 10058: 10056: 10053: 10051: 10048: 10046: 10043: 10041: 10038: 10036: 10033: 10031: 10028: 10026: 10023: 10020: 10017: 10016: 10014: 10009: 10003: 9997: 9994: 9990: 9987: 9985: 9982: 9980: 9977: 9975: 9972: 9970: 9967: 9965: 9962: 9960: 9957: 9955: 9952: 9950: 9947: 9945: 9942: 9940: 9937: 9935: 9932: 9930: 9927: 9924: 9920: 9919:pentobarbital 9916: 9913: 9909: 9906: 9904: 9901: 9899: 9896: 9894: 9891: 9889: 9886: 9884: 9881: 9879: 9876: 9874: 9871: 9869: 9866: 9864: 9861: 9859: 9856: 9854: 9853:Kaitocephalin 9851: 9849: 9846: 9844: 9841: 9839: 9836: 9834: 9831: 9829: 9826: 9824: 9821: 9819: 9816: 9814: 9811: 9809: 9806: 9803: 9802: 9799: 9796: 9794: 9791: 9789: 9786: 9784: 9781: 9779: 9776: 9774: 9771: 9769: 9766: 9764: 9761: 9759: 9756: 9754: 9751: 9749: 9746: 9744: 9741: 9739: 9736: 9734: 9731: 9729: 9726: 9724: 9721: 9719: 9716: 9714: 9711: 9709: 9706: 9704: 9701: 9699: 9696: 9694: 9691: 9689: 9686: 9684: 9681: 9679: 9676: 9674: 9673:Cyclothiazide 9671: 9669: 9666: 9662: 9659: 9657: 9654: 9652: 9649: 9647: 9646:Ibotenic acid 9644: 9642: 9639: 9637: 9634: 9632: 9629: 9627: 9624: 9622: 9619: 9617: 9614: 9611: 9608: 9607: 9605: 9600: 9594: 9590: 9587: 9580: 9575: 9573: 9568: 9566: 9561: 9560: 9557: 9539: 9536: 9534: 9531: 9529: 9526: 9524: 9521: 9519: 9516: 9514: 9511: 9509: 9506: 9505: 9504: 9501: 9500: 9498: 9496: 9492: 9489: 9487: 9483: 9479: 9467: 9461: 9459: 9453: 9452: 9451: 9448: 9447: 9445: 9443: 9439: 9431: 9428: 9426: 9423: 9421: 9418: 9416: 9413: 9411: 9408: 9406: 9403: 9401: 9398: 9396: 9393: 9391: 9388: 9387: 9386: 9383: 9382: 9380: 9378: 9374: 9366: 9363: 9361: 9358: 9356: 9353: 9351: 9348: 9346: 9343: 9342: 9341: 9338: 9335: 9332: 9330: 9327: 9325: 9322: 9320: 9316: 9313: 9312: 9310: 9308: 9304: 9301: 9299: 9296: 9292: 9282: 9279: 9278: 9276: 9274: 9270: 9264: 9257: 9255: 9244: 9242: 9236: 9234: 9224: 9222: 9212: 9209: 9208: 9205: 9202: 9200: 9197: 9195: 9192: 9190: 9187: 9185: 9182: 9180: 9177: 9175: 9172: 9170: 9167: 9165: 9162: 9160: 9157: 9155: 9152: 9150: 9147: 9145: 9142: 9140: 9137: 9135: 9132: 9129: 9128: 9126: 9124: 9120: 9114: 9111: 9109: 9103: 9101: 9095: 9093: 9087: 9085: 9079: 9078: 9076: 9074: 9070: 9062: 9056: 9054: 9048: 9046: 9040: 9039: 9038: 9031: 9027: 9024: 9022: 9019: 9017: 9014: 9012: 9009: 9007: 9001: 8999: 8993: 8991: 8985: 8983: 8977: 8975: 8969: 8967: 8961: 8959: 8953: 8951: 8945: 8943: 8937: 8935: 8929: 8927: 8921: 8919: 8913: 8912: 8911: 8905: 8904: 8902: 8900: 8896: 8888: 8885: 8883: 8880: 8878: 8875: 8873: 8870: 8868: 8865: 8864: 8863: 8857: 8856: 8854: 8852: 8848: 8845: 8843: 8839: 8835: 8831: 8827: 8820: 8815: 8813: 8808: 8806: 8801: 8800: 8797: 8791: 8789: 8786: 8782: 8780: 8777: 8775: 8772: 8769: 8768:NMDA receptor 8764: 8760: 8759: 8747: 8743: 8738: 8733: 8728: 8723: 8719: 8715: 8714:Critical Care 8711: 8704: 8696: 8692: 8687: 8682: 8678: 8674: 8670: 8666: 8662: 8655: 8649: 8646: 8640: 8634: 8628: 8620: 8616: 8611: 8606: 8602: 8598: 8594: 8587: 8579: 8575: 8571: 8567: 8563: 8559: 8555: 8551: 8544: 8542: 8533: 8527: 8512: 8508: 8504: 8500: 8496: 8492: 8488: 8481: 8473: 8469: 8464: 8459: 8455: 8451: 8447: 8440: 8432: 8428: 8424: 8420: 8416: 8412: 8408: 8404: 8397: 8389: 8385: 8380: 8375: 8371: 8367: 8363: 8359: 8355: 8348: 8346: 8337: 8330: 8322: 8315: 8307: 8303: 8298: 8293: 8289: 8285: 8281: 8274: 8266: 8262: 8258: 8254: 8250: 8246: 8242: 8238: 8234: 8230: 8223: 8215: 8211: 8205: 8201: 8200: 8192: 8184: 8180: 8175: 8170: 8166: 8162: 8158: 8154: 8150: 8143: 8135: 8131: 8125: 8121: 8120: 8112: 8104: 8100: 8095: 8090: 8086: 8082: 8078: 8074: 8070: 8066: 8062: 8055: 8047: 8043: 8039: 8035: 8031: 8027: 8020: 8018: 8016: 8014: 8005: 8001: 7997: 7991: 7987: 7983: 7976: 7968: 7964: 7960: 7956: 7952: 7948: 7944: 7940: 7933: 7925: 7921: 7917: 7913: 7909: 7905: 7901: 7897: 7893: 7889: 7882: 7874: 7870: 7865: 7860: 7856: 7852: 7848: 7844: 7840: 7833: 7825: 7821: 7816: 7811: 7807: 7803: 7799: 7795: 7791: 7787: 7783: 7776: 7768: 7764: 7759: 7754: 7749: 7744: 7740: 7736: 7732: 7728: 7724: 7717: 7715: 7706: 7702: 7697: 7692: 7688: 7684: 7680: 7676: 7672: 7665: 7657: 7653: 7649: 7645: 7641: 7637: 7633: 7629: 7622: 7614: 7610: 7605: 7600: 7595: 7590: 7586: 7582: 7578: 7571: 7563: 7559: 7555: 7551: 7547: 7543: 7539: 7535: 7528: 7520: 7516: 7511: 7506: 7502: 7498: 7494: 7490: 7486: 7479: 7471: 7467: 7462: 7457: 7453: 7449: 7445: 7441: 7437: 7430: 7422: 7418: 7413: 7408: 7404: 7400: 7396: 7392: 7388: 7381: 7373: 7369: 7365: 7361: 7357: 7353: 7346: 7338: 7334: 7330: 7326: 7322: 7318: 7314: 7310: 7302: 7294: 7290: 7286: 7282: 7278: 7274: 7270: 7266: 7259: 7257: 7255: 7253: 7244: 7240: 7235: 7230: 7225: 7220: 7216: 7212: 7208: 7201: 7193: 7189: 7184: 7179: 7175: 7171: 7167: 7163: 7159: 7152: 7146: 7142: 7138: 7137: 7130: 7122: 7118: 7113: 7108: 7104: 7100: 7096: 7089: 7081: 7077: 7072: 7067: 7063: 7059: 7055: 7048: 7040: 7036: 7031: 7026: 7022: 7018: 7014: 7010: 7006: 6999: 6991: 6987: 6983: 6979: 6975: 6971: 6967: 6963: 6956: 6948: 6944: 6939: 6934: 6929: 6924: 6920: 6916: 6912: 6908: 6904: 6897: 6889: 6885: 6881: 6877: 6873: 6869: 6862: 6854: 6850: 6845: 6840: 6835: 6830: 6826: 6822: 6818: 6811: 6803: 6799: 6795: 6791: 6787: 6783: 6779: 6775: 6767: 6759: 6755: 6751: 6747: 6743: 6739: 6735: 6731: 6723: 6715: 6711: 6706: 6701: 6697: 6693: 6689: 6682: 6674: 6670: 6666: 6662: 6658: 6654: 6650: 6646: 6639: 6637: 6628: 6624: 6620: 6616: 6611: 6606: 6602: 6598: 6594: 6587: 6585: 6570: 6566: 6559: 6551: 6547: 6542: 6537: 6533: 6529: 6525: 6521: 6517: 6510: 6503: 6501: 6494: 6486: 6482: 6477: 6472: 6468: 6464: 6460: 6456: 6452: 6445: 6437: 6433: 6429: 6425: 6421: 6417: 6409: 6401: 6397: 6393: 6389: 6385: 6381: 6377: 6373: 6366: 6358: 6354: 6349: 6344: 6340: 6336: 6332: 6325: 6323: 6314: 6310: 6306: 6302: 6298: 6294: 6291:(356): pe41. 6290: 6286: 6279: 6271: 6267: 6263: 6259: 6255: 6251: 6247: 6243: 6235: 6227: 6223: 6218: 6213: 6209: 6205: 6201: 6197: 6193: 6186: 6178: 6174: 6170: 6166: 6161: 6156: 6152: 6148: 6144: 6137: 6129: 6125: 6121: 6117: 6113: 6109: 6102: 6094: 6090: 6085: 6080: 6075: 6070: 6066: 6062: 6058: 6051: 6043: 6039: 6034: 6029: 6025: 6021: 6017: 6010: 6002: 5998: 5993: 5988: 5984: 5980: 5976: 5972: 5968: 5964: 5960: 5953: 5951: 5949: 5947: 5938: 5934: 5930: 5926: 5922: 5918: 5911: 5903: 5899: 5894: 5889: 5885: 5881: 5877: 5873: 5869: 5862: 5854: 5850: 5845: 5840: 5836: 5832: 5828: 5824: 5820: 5813: 5805: 5801: 5796: 5795:11383/1788727 5791: 5786: 5781: 5777: 5773: 5769: 5762: 5754: 5750: 5746: 5742: 5738: 5734: 5730: 5726: 5719: 5711: 5707: 5702: 5697: 5693: 5689: 5685: 5681: 5677: 5670: 5662: 5658: 5653: 5648: 5644: 5640: 5636: 5632: 5628: 5621: 5613: 5609: 5604: 5599: 5595: 5591: 5587: 5580: 5572: 5568: 5563: 5558: 5554: 5550: 5546: 5542: 5538: 5531: 5523: 5519: 5514: 5509: 5505: 5501: 5497: 5493: 5489: 5482: 5474: 5470: 5465: 5460: 5456: 5452: 5448: 5444: 5440: 5433: 5425: 5421: 5417: 5413: 5409: 5405: 5401: 5397: 5390: 5388: 5386: 5377: 5370: 5362: 5358: 5353: 5348: 5344: 5340: 5336: 5332: 5328: 5321: 5313: 5309: 5304: 5299: 5295: 5291: 5287: 5280: 5278: 5276: 5274: 5272: 5270: 5268: 5266: 5264: 5262: 5260: 5258: 5249: 5245: 5240: 5235: 5231: 5227: 5223: 5219: 5215: 5208: 5200: 5196: 5191: 5186: 5182: 5178: 5174: 5170: 5166: 5159: 5151: 5147: 5142: 5137: 5133: 5129: 5125: 5121: 5117: 5110: 5102: 5098: 5094: 5090: 5085: 5080: 5076: 5072: 5068: 5061: 5053: 5049: 5044: 5039: 5035: 5031: 5027: 5023: 5019: 5012: 5004: 5000: 4995: 4990: 4986: 4982: 4978: 4974: 4970: 4963: 4955: 4951: 4947: 4943: 4939: 4935: 4931: 4927: 4920: 4912: 4908: 4903: 4898: 4894: 4890: 4886: 4882: 4878: 4871: 4863: 4859: 4854: 4849: 4844: 4839: 4835: 4831: 4827: 4823: 4819: 4812: 4804: 4800: 4795: 4790: 4786: 4782: 4778: 4774: 4770: 4763: 4755: 4751: 4746: 4741: 4737: 4733: 4729: 4725: 4721: 4714: 4706: 4702: 4697: 4692: 4688: 4684: 4680: 4676: 4672: 4665: 4657: 4653: 4648: 4643: 4639: 4635: 4631: 4627: 4623: 4616: 4608: 4604: 4600: 4596: 4592: 4588: 4584: 4580: 4576: 4569: 4561: 4557: 4553: 4549: 4545: 4541: 4533: 4525: 4521: 4517: 4513: 4509: 4505: 4501: 4497: 4490: 4482: 4478: 4473: 4468: 4463: 4458: 4454: 4450: 4446: 4442: 4438: 4431: 4423: 4419: 4415: 4411: 4407: 4403: 4399: 4395: 4388: 4380: 4376: 4372: 4368: 4364: 4360: 4356: 4352: 4345: 4337: 4331: 4327: 4320: 4313: 4305: 4301: 4296: 4291: 4287: 4283: 4279: 4275: 4271: 4264: 4262: 4260: 4258: 4249: 4245: 4241: 4237: 4233: 4229: 4222: 4220: 4211: 4207: 4203: 4199: 4195: 4191: 4184: 4182: 4173: 4169: 4164: 4159: 4155: 4151: 4147: 4140: 4132: 4128: 4123: 4118: 4114: 4110: 4106: 4102: 4098: 4091: 4089: 4087: 4085: 4083: 4074: 4070: 4066: 4062: 4058: 4054: 4050: 4046: 4039: 4037: 4028: 4024: 4019: 4014: 4010: 4006: 4002: 3998: 3994: 3987: 3979: 3975: 3970: 3965: 3961: 3957: 3953: 3949: 3945: 3938: 3936: 3934: 3925: 3921: 3917: 3913: 3909: 3908:10.1038/nn835 3905: 3901: 3897: 3890: 3888: 3886: 3877: 3873: 3868: 3863: 3859: 3855: 3851: 3847: 3843: 3836: 3828: 3824: 3820: 3816: 3812: 3808: 3804: 3800: 3793: 3785: 3781: 3776: 3771: 3767: 3763: 3759: 3755: 3751: 3744: 3742: 3740: 3738: 3736: 3734: 3732: 3723: 3719: 3715: 3711: 3707: 3703: 3699: 3695: 3688: 3680: 3676: 3672: 3668: 3664: 3660: 3653: 3651: 3649: 3647: 3638: 3634: 3630: 3626: 3622: 3618: 3614: 3610: 3603: 3601: 3599: 3597: 3595: 3593: 3591: 3589: 3587: 3585: 3583: 3581: 3572: 3568: 3564: 3560: 3556: 3555:10.1038/nn936 3552: 3548: 3544: 3537: 3535: 3533: 3531: 3529: 3520: 3516: 3512: 3508: 3503: 3498: 3494: 3490: 3486: 3479: 3477: 3475: 3473: 3471: 3469: 3467: 3465: 3456: 3452: 3447: 3442: 3438: 3434: 3430: 3423: 3421: 3419: 3417: 3408: 3404: 3400: 3396: 3392: 3388: 3381: 3379: 3377: 3375: 3366: 3362: 3357: 3352: 3347: 3342: 3338: 3334: 3331:(5): e98079. 3330: 3326: 3322: 3315: 3307: 3303: 3298: 3293: 3289: 3285: 3281: 3277: 3273: 3266: 3258: 3254: 3250: 3246: 3242: 3238: 3231: 3224: 3222: 3213: 3209: 3205: 3201: 3197: 3193: 3189: 3185: 3178: 3170: 3166: 3162: 3158: 3151: 3143: 3139: 3135: 3131: 3127: 3120: 3118: 3109: 3105: 3101: 3097: 3093: 3089: 3085: 3081: 3077: 3073: 3066: 3058: 3054: 3049: 3044: 3040: 3036: 3032: 3028: 3024: 3017: 3009: 3005: 3001: 2997: 2993: 2989: 2985: 2981: 2977: 2973: 2966: 2964: 2950: 2946: 2942: 2938: 2931: 2923: 2919: 2915: 2911: 2906: 2901: 2897: 2893: 2889: 2882: 2874: 2870: 2865: 2860: 2856: 2852: 2848: 2844: 2840: 2833: 2831: 2823: 2819: 2815: 2810: 2805: 2801: 2797: 2793: 2786: 2784: 2779: 2770: 2767: 2766: 2760: 2758: 2754: 2750: 2746: 2742: 2741:neurotoxicity 2738: 2734: 2730: 2726: 2722: 2717: 2715: 2711: 2707: 2704: 2699: 2697: 2693: 2689: 2685: 2681: 2676: 2674: 2670: 2666: 2665:United States 2662: 2658: 2656: 2652: 2645: 2639: 2635: 2630: 2628: 2624: 2620: 2616: 2612: 2608: 2604: 2600: 2596: 2591: 2589: 2585: 2581: 2577: 2574:also produce 2573: 2572:methoxetamine 2569: 2565: 2561: 2557: 2556:nitrous oxide 2553: 2552:phencyclidine 2549: 2545: 2541: 2531: 2529: 2525: 2521: 2517: 2516:physiological 2513: 2509: 2505: 2501: 2497: 2492: 2490: 2486: 2482: 2477: 2475: 2471: 2467: 2457: 2453: 2451: 2441: 2423: 2413: 2397: 2390: 2378: 2371: 2365: 2364: 2363: 2356: 2352: 2343: 2339: 2337: 2332: 2330: 2326: 2317: 2313: 2304: 2297: 2293: 2284: 2282: 2277: 2268: 2266: 2262: 2248: 2244: 2240: 2235: 2232: 2228: 2225: 2221: 2217: 2213: 2209: 2205: 2202: 2199: 2196: 2192: 2189: 2186: 2182: 2178: 2175: 2172: 2169: 2166: 2162: 2158: 2154: 2150: 2147: 2144: 2141: 2138: 2134: 2130: 2127: 2124: 2121: 2120: 2119: 2117: 2113: 2096: 2095: 2090: 2087: 2084: 2081: 2080: 2079: 2077: 2066: 2062: 2058: 2056: 2051: 2047: 2039: 2034: 2033:nitrosylation 2022: 2018: 2015: 2013: 2009: 2006: 2003: 2000: 1997: 1994: 1991: 1990:antiaddictive 1987: 1983: 1980: 1977: 1973: 1969: 1966: 1964: 1960: 1957: 1954: 1950: 1946: 1942: 1938: 1935: 1933: 1929: 1926: 1921: 1915: 1911: 1908: 1905: 1901: 1897: 1894: 1893: 1892: 1886: 1883: 1880: 1877: 1874: 1871: 1868: 1865: 1862: 1861:Psychotridine 1859: 1856: 1855:Phenylalanine 1853: 1850: 1849:Phencyclidine 1847: 1844: 1841: 1838: 1835: 1828: 1827:Nitrous oxide 1825: 1822: 1819: 1816: 1815:Methoxetamine 1813: 1810: 1807: 1804: 1801: 1798: 1795: 1792: 1789: 1786: 1783: 1781: 1780: 1775: 1774:Kaitocephalin 1772: 1769: 1766: 1763: 1760: 1757: 1754: 1751: 1748: 1745: 1742: 1739: 1736: 1733: 1732:Diethyl ether 1730: 1727: 1724: 1721: 1718: 1716: 1712: 1709: 1707: 1703: 1700: 1697: 1693: 1690: 1687: 1684: 1681: 1678: 1675: 1672: 1669: 1668: 1663: 1660: 1657: 1654: 1651: 1648: 1646: 1642: 1639: 1638: 1637: 1629: 1627: 1623: 1622:uncompetitive 1618: 1616: 1612: 1608: 1607:phencyclidine 1604: 1600: 1596: 1592: 1588: 1585:due to their 1584: 1580: 1572: 1568: 1563: 1550: 1547: 1544: 1541: 1538: 1535: 1534: 1533: 1527: 1521: 1517: 1514: 1511: 1508: 1505: 1503: 1502: 1497: 1490: 1487: 1484: 1481: 1480: 1474: 1472: 1468: 1463: 1461: 1457: 1453: 1452:schizophrenia 1445: 1433: 1431: 1425: 1417: 1411: 1406: 1397: 1395: 1391: 1387: 1383: 1375: 1371: 1357: 1354: 1351: 1348: 1347: 1345: 1340: 1337: 1334: 1331: 1328: 1325: 1322: 1319: 1316: 1313: 1310: 1309:Cerebrosterol 1307: 1306: 1305: 1302: 1295: 1288: 1281: 1278: 1275: 1272: 1270: 1266: 1263: 1260: 1253: 1246: 1243: 1242: 1240: 1237: 1232: 1229: 1227: 1226: 1221: 1220:Ibotenic acid 1218: 1215: 1212: 1209: 1206: 1205: 1203: 1202:Glutamic acid 1200: 1189: 1185: 1178: 1172:(aspartate) ( 1171: 1170:Aspartic acid 1168: 1167: 1165: 1162: 1161: 1160: 1152: 1150: 1146: 1142: 1138: 1133: 1131: 1119: 1115: 1108: 1106: 1103: 1099: 1095: 1087: 1083: 1076: 1075:Glutamic acid 1068: 1054: 1052: 1048: 1044: 1039: 1029: 1027: 1021: 1019: 1014: 1004: 1001: 997: 986: 984: 980: 976: 971: 969: 965: 960: 950: 947: 943: 939: 935: 931: 921: 912: 910: 906: 901: 893: 890: 887: 886: 885: 882: 880: 875: 871: 862: 853: 851: 848: 845: 841: 837: 833: 829: 825: 821: 818: 814: 810: 806: 802: 798: 794: 790: 786: 782: 778: 775: 766: 754: 751: 748: 745: 744: 743: 741: 737: 722: 719: 715: 712: 708: 704: 700: 695: 691: 689: 685: 681: 677: 667: 665: 656: 652: 648: 644: 641: 637: 633: 630: 626: 622: 619: 615: 614: 611: 610:extracellular 606: 605: 604: 601: 599: 595: 591: 586: 582: 580: 574: 571: 567: 566:AMPA receptor 563: 552: 548: 544: 542: 538: 534: 529: 525: 521: 517: 509: 505: 492: 488: 486: 482: 481: 479: 475: 471: 469: 465: 463: 459: 457: 453: 452: 450: 448: 444: 443: 442: 440: 436: 432: 428: 419: 410: 408: 404: 399: 395: 390: 388: 384: 380: 375: 374:Hilmar Bading 370: 368: 364: 360: 356: 352: 348: 343: 335: 325: 323: 318: 314: 310: 305: 300: 298: 294: 290: 286: 278: 274: 270: 266: 265:neurotoxicity 262: 258: 254: 250: 242: 238: 235: 231: 227: 223: 219: 218:nitrous oxide 215: 211: 207: 203: 199: 195: 191: 190:phencyclidine 187: 182: 179: 175: 171: 167: 161: 156: 152: 147: 145: 141: 137: 133: 132:cell membrane 129: 124: 120: 113: 109: 105: 101: 97: 93: 89: 85: 81: 77: 73: 72:NMDA receptor 69: 66: 60: 52: 48: 44: 40: 35: 29: 22: 12268:Ion channels 11938: 11926: 11907:Lateral line 11857:Waggle dance 11795:Eric Knudsen 11682: 11660: 11592: 11585: 11576: 11575: 11559: 11556: 11428: 11335:Cyclopropane 11316: 11299: 11277: 11213: 11165:Propoxyphene 11135:Orphenadrine 11040:Ketobemidone 11005:Eticyclidine 10940:Coronaridine 10925:ARL-15896-AR 10841: 10809: 10721:-Cycloserine 10703:Carisoprodol 10659: 10547: 10545:Antagonists: 10544: 10477: 10472: 10455: 10383:-Cycloserine 10324: 10263: 10260: 10204:Barbiturates 10200: 10177:Selurampanel 10132:Dasolampanel 10119:Antagonists: 10118: 10088: 10021: 10018: 9992: 9929:Cyclopropane 9915:Barbiturates 9911: 9883:Selurampanel 9833:Dasolampanel 9805:Antagonists: 9804: 9788:Pramiracetam 9664: 9612: 9609: 9485: 9449: 9441: 9384: 9376: 9306: 9272: 9210: 9130: 8787: 8784: 8717: 8713: 8703: 8668: 8664: 8654: 8639: 8627: 8600: 8596: 8586: 8556:(1): 15–26. 8553: 8549: 8526:cite journal 8515:. Retrieved 8497:(1): 29–41. 8494: 8490: 8480: 8453: 8449: 8439: 8406: 8402: 8396: 8361: 8357: 8329: 8314: 8287: 8283: 8273: 8232: 8228: 8222: 8214:the original 8199:Neuroscience 8198: 8191: 8156: 8152: 8142: 8134:the original 8119:Neuroscience 8118: 8111: 8068: 8064: 8054: 8029: 8025: 7985: 7975: 7942: 7938: 7932: 7891: 7887: 7881: 7846: 7842: 7832: 7789: 7785: 7775: 7730: 7726: 7678: 7674: 7664: 7631: 7627: 7621: 7584: 7580: 7570: 7537: 7533: 7527: 7492: 7488: 7478: 7443: 7439: 7429: 7394: 7390: 7380: 7355: 7351: 7345: 7312: 7308: 7301: 7268: 7264: 7214: 7210: 7200: 7165: 7161: 7151: 7140: 7134: 7129: 7102: 7098: 7088: 7061: 7057: 7047: 7012: 7008: 6998: 6965: 6961: 6955: 6910: 6906: 6896: 6871: 6867: 6861: 6824: 6820: 6810: 6777: 6773: 6766: 6736:(1): 71–77. 6733: 6729: 6722: 6695: 6691: 6681: 6651:(1): 64–82. 6648: 6644: 6600: 6596: 6572:. Retrieved 6568: 6558: 6523: 6519: 6509: 6499: 6493: 6458: 6454: 6444: 6419: 6415: 6408: 6375: 6371: 6365: 6338: 6334: 6288: 6284: 6278: 6245: 6241: 6234: 6199: 6195: 6185: 6150: 6146: 6136: 6111: 6107: 6101: 6064: 6060: 6050: 6023: 6019: 6009: 5966: 5962: 5920: 5916: 5910: 5878:(1): 68–87. 5875: 5872:Neuroscience 5871: 5861: 5829:(1): 62–75. 5826: 5822: 5812: 5775: 5771: 5761: 5728: 5724: 5718: 5683: 5679: 5669: 5634: 5630: 5620: 5593: 5589: 5579: 5544: 5540: 5530: 5495: 5491: 5481: 5446: 5442: 5432: 5402:(2): 81–89. 5399: 5395: 5375: 5369: 5334: 5330: 5320: 5293: 5289: 5221: 5217: 5207: 5172: 5168: 5158: 5123: 5119: 5109: 5074: 5070: 5060: 5025: 5021: 5011: 4976: 4972: 4962: 4932:(4): 62–68. 4929: 4925: 4919: 4884: 4880: 4870: 4825: 4821: 4811: 4776: 4772: 4762: 4727: 4723: 4713: 4678: 4674: 4664: 4629: 4625: 4615: 4582: 4578: 4568: 4543: 4539: 4532: 4499: 4495: 4489: 4444: 4440: 4430: 4397: 4393: 4387: 4354: 4350: 4344: 4325: 4312: 4277: 4273: 4234:(1): 48–55. 4231: 4227: 4196:(1): 55–85. 4193: 4189: 4153: 4149: 4139: 4104: 4100: 4048: 4044: 4000: 3996: 3986: 3951: 3947: 3899: 3895: 3849: 3845: 3835: 3802: 3798: 3792: 3757: 3753: 3697: 3694:Neuroscience 3693: 3687: 3662: 3658: 3612: 3608: 3546: 3542: 3492: 3488: 3436: 3432: 3393:(1): 61–67. 3390: 3386: 3328: 3324: 3314: 3279: 3275: 3265: 3243:(1): 39–47. 3240: 3236: 3187: 3183: 3177: 3160: 3156: 3150: 3133: 3129: 3075: 3071: 3065: 3030: 3026: 3016: 2975: 2971: 2952:, retrieved 2940: 2930: 2895: 2891: 2881: 2846: 2842: 2821: 2799: 2795: 2718: 2703:dopaminergic 2701:Compared to 2700: 2677: 2659: 2631: 2621:, including 2607:zelquistinel 2605:(NRX-1074), 2592: 2576:dissociative 2562:are used as 2537: 2524:pathological 2493: 2478: 2463: 2454: 2447: 2419: 2386: 2360: 2354: 2340: 2333: 2325:dopaminergic 2321: 2315: 2301: 2295: 2274: 2257: 2109: 2092: 2074: 2064: 2030: 1996:Ketobemidone 1986:hallucinogen 1976:antidementia 1890: 1777: 1695: 1665: 1635: 1619: 1595:brain damage 1591:dissociation 1576: 1537:Zelquistinel 1531: 1519: 1499: 1496:-cycloserine 1464: 1435:3,5-Dibromo- 1434: 1423: 1421: 1409: 1386:cyclohexanes 1379: 1373: 1223: 1187: 1158: 1134: 1129: 1109: 1091: 1046: 1035: 1025: 1022: 1010: 992: 972: 956: 927: 918: 897: 883: 867: 809:growth cones 774:invertebrate 771: 733: 716: 696: 692: 680:permeability 673: 660: 646: 635: 624: 608: 602: 587: 583: 575: 556: 550: 537:binding site 513: 507: 438: 434: 430: 426: 424: 403:hypoglycemic 391: 371: 367:Huntington's 342:Jeff Watkins 333: 331: 301: 277:astrogliosis 241:cannabinoids 186:psychoactive 183: 159: 148: 75: 71: 67: 58: 57: 55: 12227:antagonists 12012:Preclinical 12002:Hit to lead 11983:Drug design 11831:Patch clamp 11800:Eric Kandel 11780:Franz Huber 11651:Feedforward 11525:Pentamidine 11510:Minocycline 11490:Hodgkinsine 11460:Dexanabinol 11390:Sevoflurane 11244:Isoxsuprine 11239:Haloperidol 11219:Besonprodil 11180:Rimantadine 11130:Norketamine 11125:Noribogaine 11100:Milnacipran 11065:Levorphanol 11015:Gacyclidine 10985:Dizocilpine 10980:Diphenidine 10970:Dextrorphan 10890:Alaproclate 10833:Huperzine A 10786:Meprobamate 10746:Harkoseride 10641:Perzinfotel 10518:Plazinemdor 10065:Kainic acid 10050:Domoic acid 9996:Minocycline 9984:Sevoflurane 9661:Willardiine 9636:Domoic acid 8826:Ion channel 8032:(1): 1–17. 7136:NCT00188383 6774:Amino Acids 6603:(12): 897. 6067:: 1156777. 5969:(1): 4966. 3136:(1): 7–61. 2615:rislenemdaz 2603:apimostinel 2601:(GLYX-13), 2472:in various 2389:patch-clamp 2276:Competitive 2243:lipoic acid 2239:glutathione 2165:hippocampus 2118:compounds: 2089:Conantokins 2046:hypotension 2008:Minocycline 1968:Huperzine A 1963:expectorant 1959:Guaifenesin 1910:Atomoxetine 1879:Traxoprodil 1843:Perzinfotel 1762:Hodgkinsine 1744:Dizocilpine 1738:Diphenidine 1726:Dexanabinol 1720:Dextrorphan 1715:dextrorphan 1611:dextrorphan 1579:anesthetics 1556:Antagonists 1543:Apimostinel 1489:Cycloserine 1471:apimostinel 1346:Polyamines 1315:Cholesterol 1198:-aspartate. 1164:Amino acids 900:excitotoxic 879:doogie mice 842:and across 781:vertebrates 640:conductance 520:ion channel 363:Alzheimer's 359:Parkinson's 309:glutathione 206:anaesthetic 204:(DXM). The 146:functions. 84:ion channel 49:and two of 12252:Categories 12118:Gliflozins 11805:Nobuo Suga 11720:in insects 11563:AGN-241751 11535:Piretanide 11485:Furosemide 11470:Flupirtine 11447:Conantokin 11442:Caroverine 11437:Bumetanide 11370:Isoflurane 11340:Desflurane 11330:Chloroform 11269:Safaprodil 11264:Ro 25-6981 11205:Tiletamine 11190:Sabeluzole 11170:Remacemide 11115:Neramexane 11085:Methorphan 11070:Loperamide 11045:Lanicemine 11030:Indantadol 10995:Esketamine 10990:Ephenidine 10950:Dexoxadrol 10915:Arketamine 10900:Amantadine 10860:3-MeO-PCMo 10838:Putrescine 10781:MDL-105519 10756:Kynurenine 10736:Gavestinel 10651:SDZ-220581 10611:MDL-100453 10494:prasterone 10464:Spermidine 10437:Milacemide 10342:ACC (ACPC) 10228:Evans blue 10192:Topiramate 10182:Tezampanel 10112:Isoflurane 9989:Talampanel 9974:Perampanel 9969:Isoflurane 9954:GYKI-53655 9949:GYKI-52466 9944:Evans blue 9908:Zonampanel 9898:Topiramate 9888:Tezampanel 9863:Kynurenine 9823:Caroverine 9818:Becampanel 9768:Oxiracetam 9668:Aniracetam 9589:modulators 9298:glutamates 9295:Ionotropic 9211:pentamers: 8785:Drosophila 8720:(1): 427. 8517:2020-04-12 6574:2008-12-17 6341:: 109654. 4156:: 109654. 2954:2024-03-04 2941:StatPearls 2775:References 2739:-mediated 2729:licostinel 2725:gavestinel 2706:stimulants 2684:autoimmune 2634:tianeptine 2599:rapastinel 2595:esketamine 2584:euphoriant 2548:tiletamine 2544:esketamine 2508:endogenous 2504:micromolar 2500:millimolar 2487:(LTP) and 2265:anesthesia 2143:Polyamines 2112:endogenous 2101:Modulators 2038:neurotoxic 2012:antibiotic 1953:anxiolytic 1945:euphoriant 1896:Amantadine 1873:Tiletamine 1797:Lanicemine 1768:Ifenprodil 1756:Esketamine 1702:Delucemine 1549:Rapastinel 1467:rapastinel 1382:neramexane 1365:Neramexane 1350:Spermidine 1333:Nebostinel 1265:Milacemide 1102:co-agonist 813:ifenprodil 707:amantadine 579:antagonist 568:-mediated 394:amantadine 166:-aspartate 151:ionotropic 65:-aspartate 11577:See also: 11557:Unsorted: 11500:MDL-27266 11480:FR-115427 11475:FPL-12495 11432:ARR-15896 11360:Halothane 11350:Enflurane 11308:Magnesium 11259:Ro 8-4304 11234:Eliprodil 11145:PD-137889 11105:Morphanol 11080:Methadone 11075:Memantine 11025:Ibogamine 11000:Etoxadrol 10930:ARL-16247 10920:ARL-12495 10905:Aptiganel 10870:4-MeO-PCP 10865:3-MeO-PCP 10855:3-MeO-PCE 10818:Co 101676 10791:MRZ 2/576 10741:GV-196771 10731:Felbamate 10708:CGP-39653 10688:ACEA-1328 10683:ACEA-1011 10626:NPC-17742 10621:NPC-12626 10606:LY-274614 10601:LY-235959 10596:LY-233053 10581:CGS-19755 10576:CGP-40116 10571:CGP-39653 10566:CGP-39551 10561:CGP-37849 10551:AP5 (APV) 10452:Sarcosine 10328:β-Fluoro- 10277:Glutamate 10272:Aspartate 10261:Agonists: 10218:Enflurane 10162:LY-382884 10122:ACEA-1011 10107:Halothane 10102:Enflurane 10097:Diazoxide 10070:LY-339434 10055:Glutamate 10019:Agonists: 9964:Irampanel 9959:Halothane 9934:Enflurane 9808:ACEA-1011 9783:Piracetam 9763:ORG-26576 9758:Nooglutyl 9748:LY-503430 9743:LY-451646 9738:LY-404187 9733:LY-395153 9728:LY-392098 9713:Diazoxide 9641:Glutamate 9610:Agonists: 9131:monomers: 8550:CNS Drugs 8306:2168-9709 8290:(5): 56. 8071:: 14781. 5731:: 10–16. 4073:222210921 2914:1802-9973 2721:eliprodil 2686:disease, 2661:Memantine 2638:glutamate 2512:exogenous 2355:Figure 8: 2316:Figure 5: 2296:Figure 4: 2116:exogenous 2078:include: 2065:Figure 7: 2002:Methadone 1900:antiviral 1821:Midafotel 1809:Memantine 1803:LY-235959 1750:Eliprodil 1686:CGP-37849 1374:Figure 6: 1274:Sarcosine 1098:aspartate 1094:glutamate 905:lethality 850:evolution 805:glutamate 777:organisms 718:Memantine 711:memantine 688:glutamate 551:Figure 2: 516:glutamate 508:Figure 1: 489:GluN3B – 483:GluN3A – 472:GluN2D – 466:GluN2C – 460:GluN2B – 454:GluN2A – 413:Structure 322:Memantine 293:memantine 273:astrocyte 263:-induced 222:cytosolic 210:analgesic 157:molecule 108:glutamate 86:found in 47:aspartate 43:glutamate 12188:Triptans 12073:agonists 12017:Clinical 11928:Category 11668:Instinct 11644:Concepts 11505:Metaphit 11415:Urethane 11303:Hydrogen 11300:Cations: 11210:Tramadol 11035:Ketamine 11020:Ibogaine 10935:Budipine 10850:3-HO-PCP 10776:LU-73068 10766:L-701324 10761:L-689560 10668:5,7-DCKA 10656:Selfotel 10538:SAGE-718 10533:SAGE-301 10528:SAGE-201 10469:Spermine 10459:Neomycin 10424:-Alanine 10416:L-687414 10375:-Alanine 10332:-alanine 10321:Theanine 10187:Theanine 10085:SYM-2081 9893:Theanine 9442:‘Orphan’ 8746:31888772 8695:18395805 8619:16829947 8578:30330824 8570:18072812 8511:18221189 8472:15753957 8431:21953270 8423:15550348 8388:19704408 8183:15240809 8103:26477507 8046:15519530 8004:21204415 7967:10324716 7873:23959708 7824:11118151 7767:21135233 7705:20375082 7648:11600628 7613:35022040 7587:(1): 8. 7562:39275755 7519:16148228 7470:18184784 7421:17529984 7372:15670959 7337:25871948 7293:34931289 7285:17882256 7243:28616020 7192:20423340 7121:15634735 7080:11986979 7039:21677647 6990:36689761 6888:10903397 6853:26257776 6794:11026487 6758:38065910 6750:12363406 6714:10785653 6673:31914015 6665:23237916 6627:33113283 6619:24287771 6550:30544218 6485:20050189 6436:18221208 6400:11672391 6392:15687225 6357:37437688 6313:39125762 6305:17033043 6270:13505187 6262:15703381 6226:31959360 6177:12987037 6169:20152125 6128:13443577 6093:37292368 6084:10244591 6042:23535319 6001:33009404 5937:21310659 5902:20096331 5853:22343826 5804:22863013 5745:23270879 5710:21543591 5661:22325859 5612:23452857 5571:19625523 5522:24285894 5473:20720132 5424:26207057 5416:12536131 5312:24742457 5248:19244516 5199:18322077 5150:17881522 5052:16540573 5003:17360906 4954:10789248 4911:15470155 4862:26636753 4803:24408959 4754:30082915 4705:29351585 4656:23439125 4607:18582691 4599:24464409 4560:18586028 4516:19738623 4481:20976280 4441:PLOS ONE 4422:24875113 4414:17052219 4379:14852616 4371:12973747 4304:23421676 4248:17097347 4210:12493535 4172:37437688 4131:23432396 4065:33033186 4027:28209726 3978:20842175 3916:11953750 3876:16402093 3827:24726102 3819:10465381 3784:15717010 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11845:Systems 11824:Methods 11549:saffron 11395:Toluene 11385:Octanol 11365:Hexanol 11320:Benzene 11296:TCN-213 11291:TCN-201 11286:MPX-007 11281:MPX-004 10875:8A-PDHQ 10813:Arcaine 10806:ZD-9379 10503:sulfate 10432:-Serine 10406:Glycine 10391:-Serine 10306:Proline 10233:NS-3763 10206:(e.g., 10197:UBP-302 10075:Proline 9917:(e.g., 9793:S-18986 9723:IDRA-21 9708:CX-1942 9703:CX-1739 9651:Proline 9340:Kainate 9073:Glycine 8737:6937792 8686:2680493 8379:2902200 8265:4344173 8257:6320006 8237:Bibcode 8174:6729657 8094:4609936 8073:Bibcode 7959:2696504 7924:4351139 7916:1692970 7896:Bibcode 7864:3744042 7815:2175035 7794:Bibcode 7786:Science 7758:3009822 7735:Bibcode 7696:2886862 7656:6141092 7604:8756626 7554:9005855 7534:Science 7510:6725528 7461:6670547 7412:3910113 7329:1328523 7234:5461601 7183:2874851 7030:3171209 6982:8242387 6947:2556719 6915:Bibcode 6844:4529710 6802:2899648 6541:6403082 6476:2807662 6217:7092371 5992:7532172 5971:Bibcode 5893:2840201 5844:3567917 5753:7836184 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