title: [NMDA-type glutamate receptor and schizophrenia].
abstract: Reduced glutamate neurotransmission via the NMDA receptor has been hypothesized to be involved in the pathophysiology of schizophrenia chiefly based upon the following observations: (1) non-competitive and competitive antagonists for the NMDA receptor including phencyclidine mimic not only positive symptoms but also negative and cognitive symptoms of schizophrenia, (2) the rank order potency of schizophrenomimetic effects of NMDA receptor antagonists is strictly correlated with that of their NMDA receptor-current blocking efficacies, (3) non-psychotomimetic doses of NMDA receptor antagonists for healthy controls produce psychotic symptoms in the remitted patients with schizophrenia, and (4) a schizophrenia-like psychotic state has often been reported in patients with encephalitis with anti-NMDA receptor antibody in the central nervous system. The possible NMDA receptor hypofunction could be caused by understimulation of its glycine site and/or by loss of NMDA receptor-possessing cells due to excess synaptic glutamate contents, or could lead to overactivation of the non-NMDA glutamate receptors. Therefore, agents for direct or indirect facilitation of the glycine site function or for attenuation of glutamate release have been studied to develop a novel pharmacotherapy for schizophrenia that could ameliorate both its antipsychotic-responsive and -resistant symptoms.
authors: Toru
authors: T
authors: Nishikawa
authors: Sayuri
authors: S
authors: Ishiwata
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D058990:Molecular Targeted Therapy; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D014150:Antipsychotic Agents; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid