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).
^"N-Methylaspartate - Compound Summary".PubChem Compound. USA: National Center for Biotechnology Information. 24 June 2005. Identification. Retrieved9 January 2012.
^Watkins, J. C. (November 1962). "The synthesis of some acidic amino acids possessing neuropharmacological activity".Journal of Medicinal and Pharmaceutical Chemistry.5 (6):1187–1199.doi:10.1021/jm01241a010.ISSN1520-4804.PMID14056452.
^Todoroki, Natsumi; Shibata, Kimihiko; Yamada, Takahiro; Kera, Yoshio; Yamada, Ryo-hei (May 1999). "Determination ofN-methyl-D-aspartic in tissues of bivalves by high-performance liquid chromatography".Journal of Chromatography B: Biomedical Sciences and Applications.728 (1):41–47.doi:10.1016/S0378-4347(99)00089-4.ISSN0378-4347.PMID10379655.
^D'Aniello, Antimo; De Simone, Antonella; Spinelli, Patrizia; D'Aniello, Salvatore; Branno, Margherita; Aniello, Francesco; Rios, Jeannette; Tsesarskaja, Mara; Fisher, George (September 2002). "A specific enzymatic high-performance liquid chromatography method to determineN-methyl-D-aspartic acid in biological tissues".Analytical Biochemistry.308 (1):42–51.doi:10.1016/S0003-2697(02)00326-3.ISSN0003-2697.PMID12234462.
^Johnson, Patricia I.; Parente, Mary Ann; Stellar, James R. (May 1996). "NMDA-induced lesions of the nucleus accumbens or the ventral pallidum increase the rewarding efficacy of food to deprived rats".Brain Research.722 (1–2):109–117.doi:10.1016/0006-8993(96)00202-8.ISSN0006-8993.PMID8813355.S2CID23002111.
