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| Names | |
|---|---|
| IUPAC name N-Methyl-D-aspartic acid | |
| Systematic IUPAC name (2R)-2-(Methylamino)butanedioic acid[1] | |
| Other names N-Methylaspartate;N-Methyl-D-aspartate; NMDA | |
| Identifiers | |
3D model (JSmol) | |
| 1724431 | |
| ChEBI | |
| ChEMBL | |
| ChemSpider |
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| KEGG |
|
| MeSH | N-Methylaspartate |
| RTECS number |
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| UNII | |
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| Properties | |
| C5H9NO4 | |
| Molar mass | 147.130 g·mol−1 |
| Appearance | White, opaque crystals |
| Odor | Odorless |
| Melting point | 189 to 190 °C (372 to 374 °F; 462 to 463 K) |
| logP | 1.39 |
| Acidity (pKa) | 2.206 |
| Basicity (pKb) | 11.791 |
| Hazards | |
| Lethal dose or concentration (LD, LC): | |
LD50 (median dose) | 137 mg kg−1 (intraperitoneal, mouse) |
| Related compounds | |
Related amino acid derivatives | |
Related compounds | Dimethylacetamide |
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |
N-methyl-D-aspartic acid, orN-methyl-D-aspartate (NMDA), is anamino acid derivative that acts as a specificagonist at theNMDA receptor mimicking the action ofglutamate, theneurotransmitter which normally acts at that receptor. Unlike glutamate, NMDA only binds to and regulates the NMDA receptor and has no effect on other glutamate receptors (such as those forAMPA andkainate). NMDA receptors are particularly important when they become overactive during, for example,alcohol withdrawal, as this causes symptoms such asagitation and, sometimes, epileptiformseizures.[citation needed]
In 1962, J.C. Watkins reported synthesizing NMDA, anisomer of the previously knownN-Methyl-DL-aspartic-acid.[2][3] NMDA is a water-solubleD-alpha-amino acid — anaspartic acid derivative with anN-methyl substituent andD-configuration — found acrossChordates fromlancelets tomammals.[4][5] At homeostatic levels NMDA plays an essential role as a neurotransmitter and neuroendocrine regulator.[6] At increased but sub–toxic levels NMDA becomesneuroprotective.[citation needed] In excessive amounts NMDA is an excitotoxin. Behavioral neuroscience research utilizes NMDAexcitotoxicity to induce lesions in specific regions of ananimal subject's brain or spinal cord to study behavioral changes.[7]
The mechanism of action for theNMDA receptor is a specific agonist binding to its NR2 subunits, and then a non-specific cation channel is opened, which can allow the passage of Ca2+ and Na+ into the cell and K+ out of the cell. Therefore, NMDA receptors will only open if glutamate is in the synapse and concurrently the postsynaptic membrane is already depolarized - acting ascoincidence detectors at the neuronal level.[8] Theexcitatory postsynaptic potential (EPSP) produced by activation of an NMDA receptor also increases the concentration of Ca2+ in the cell. The Ca2+ can in turn function as a second messenger in various signaling pathways.[9][10][11][12] This process is modulated by a number of endogenous and exogenous compounds and plays a key role in a wide range of physiological (such as memory) and pathological processes (such asexcitotoxicity).
Examples ofantagonists, or more appropriately named receptor channel blockers, of the NMDA receptor areAPV,amantadine,dextromethorphan (DXM),ketamine, magnesium,[13]tiletamine,phencyclidine (PCP),riluzole,memantine,methoxetamine (MXE),methoxphenidine (MXP) andkynurenic acid. Whiledizocilpine is generally considered to be the prototypical NMDA receptor blocker and is the most common agent used in research, animal studies have demonstrated some amount ofneurotoxicity, which may or may not also occur in humans. These compounds are commonly referred to asNMDA receptor antagonists.
