NMDA Receptor - Clinical Significance

Clinical Significance

Cochlear NMDARs are the target of intense research to find pharmacological solutions to treat tinnitus. Recently, NMDARs were associated with a rare autoimmune disease, Anti-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 teratoma.

Antagonizing the NMDA receptor with the Drug Memantine (Namenda(R)) has shown some benefit in treating Alzheimer's Dementia.

D-amino acid oxidase (DAO), an FAD-dependent peroxisomal enzyme that catalyzes oxidative deamination of D-amino acids, which are found in plants and the cell walls of microorganisms. One such D-amino acid is D-serine, which is the isomeric form of serine that modulates NMDA-type glutamate receptors as a full agonist of the glycine site on these receptors. Increased DAO activity has been linked to increased susceptibility to schizophrenia, which may result from a decreased modulation of these NMDA receptors as a result of decreased D-serine. Additionally, increased administration of D-serine with nonclozapine antipsychotics has demonstrated improved positive, negative, and cognitive symptoms, whereas the partial agonist d-cycloserine improved negative symptoms of patients taking conventional antipsychotics but worsened symptoms in clozapine-treated patients. Administration of D-serine with clozapine, on the other hand, demonstrated no improvement or worsening of symptoms, as previously demonstrated with d-cycloserine, suggesting either that clozapine may have an agonistic effect on the NMDA system or that clozapine-treated patients do not respond to d-serine.