N-Methyl-D-aspartic acid

N-Methyl-D-aspartic acid or N-Methyl-D-aspartate (NMDA) is an amino acid derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate, the neurotransmitter 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 for AMPA and kainate). NMDA receptors are particularly important when they become overactive during withdrawal from alcohol as this causes symptoms such as agitation and, sometimes, epileptiform seizures.

Biological function

NMDA is a water-soluble synthetic substance that is not normally found in biological tissue. It was first synthesized in 1960s. NMDA is an excitotoxin (it kills nerve cells by over-exciting them); this trait has applications in behavioral neuroscience research. The body of work utilizing this technique falls under the term "lesion studies." Researchers apply NMDA to specific regions of an (animal) subject's brain or spinal cord and subsequently test for the behavior of interest, such as operant behavior. If the behavior is compromised, it suggests the destroyed tissue was part of a brain region that made an important contribution to the normal expression of that behavior.

However, in lower quantities NMDA is not neurotoxic. In fact, normal operation of the NMDA receptor allows individuals to respond to excitatory stimuli through the interrelated functioning of NMDA receptors, glutamate, and dopamine.

Therefore the action of glutamate specifically through NMDA receptors can be investigated by injecting small quantities of NMDA into a certain region in the brain: for example, injection of NMDA in a brainstem region induces involuntary locomotion in cats and rats.

Antagonists

Examples of antagonists of the NMDA receptor are APV, Amantadine, dextromethorphan, ketamine, phencyclidine (PCP), riluzole, memantine, and kynurenic acid; the latter is the only known endogenous antagonist. They are commonly referred to as NMDA receptor antagonists.

References

• Watkins, Jeffrey C.; Jane, David E. (2006), "The glutamate story", Br. J. Pharmacol. 147 (Suppl. 1): S100–8, doi:10.1038/sj.bjp.0706444, PMC 1760733, PMID 16402093, http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1760733 .

Further reading

• Blaise, Mathias-Costa; Sowdhamini, Ramanathan; Rao, Metpally Raghu Prasad; Pradhan, Nithyananda (2004), "Evolutionary trace analysis of ionotropic glutamate receptor sequences and modeling the interactions of agonists with different NMDA receptor subunits", J. Mol. Model. 10 (5-6): 305–16, doi:10.1007/s00894-004-0196-7, PMID 15597199 .