[Glutamate hypothesis of schizophrenia and targets for new antipsychotic drugs].
N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine (PCP) and ketamine have been known to cause schizophrenia-like psychosis (positive symptoms, negative symptoms, cognitive dysfunction) in humans. A dysfunction of glutamatergic neurotransmission may play an important role in the pathophysiology of schizophrenia. In this review, the glutamate hypothesis of schizophrenia, especially the mechanism of neurotoxicity of NMDA receptor antagonist in the posterior cingulate cortex and retrosplenial cortex of the brain, is summarized. Furthermore, the roles of the posterior cingulate cortex and the retrosplenial cortex in the pathophysiology of schizophrenia and Alzheimer's disease are also discussed. Moreover, the glycine site of the NMDA receptor, metabotropic glutamate receptor, AMPA receptor, and antioxidant glutathione as novel potential targets for the treatment of schizophrenia are discussed.
Hashimoto
Kenji
K
Department of Psychiatry, Graduate School of Medicine, Chiba University, 1-8-1, Inohana, Chiba, 260-8670 Japan.
Iyo
Masaomi
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003337:Corpus Callosum / Q000187:drug effects / Q000502:physiology; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors / Q000633:toxicity; D015195:Drug Design; D005971:Glutamates / Q000502:physiology*; D005978:Glutathione; D005998:Glycine / Q000037:antagonists & inhibitors; D006179:Gyrus Cinguli / Q000187:drug effects / Q000502:physiology; D006801:Humans; D010622:Phencyclidine / Q000037:antagonists & inhibitors / Q000633:toxicity; D018091:Receptors, AMPA / Q000187:drug effects; D017470:Receptors, Glutamate / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012559:Schizophrenia / Q000188:drug therapy / Q000209:etiology*; D009435:Synaptic Transmission / Q000502:physiology
D014150:Antipsychotic Agents; D005971:Glutamates; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D005978:Glutathione; D010622:Phencyclidine; D005998:Glycine