Glycine transporter inhibitors as therapeutic agents for schizophrenia.
Multiple lines of evidence suggest that a dysfunction in the glutamatergic neurotransmission via the N-methyl-D-aspartate (NMDA) receptors contributes to the pathophysiology of psychiatric diseases including schizophrenia. The potentiation of NMDA receptor function may be a useful approach for the treatment of diseases associated with NMDA receptor hypofunction. One possible strategy is to increase synaptic levels of glycine by blocking the glycine transporter-1 (GlyT-1) in glia cells, since glycine acts as a co-agonist site on the NMDA receptor. In this article, the author reviews the recent important patents on GlyT-1 inhibitors for treatment of schizophrenia and other psychiatric diseases associated with the NMDA receptor hypofunction.
Hashimoto
Kenji
K
Division of Clinical Neuroscience, Chiba University Center for Forensic Mental Health, Chiba 260-8670, Japan. hashimoto@faculty.chiba-u.jp
D000818:Animals; D001549:Benzamides / Q000627:therapeutic use; D018698:Glutamic Acid / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives; D050487:Glycine Plasma Membrane Transport Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D010880:Piperidines / Q000627:therapeutic use; D012559:Schizophrenia / Q000188:drug therapy* / Q000209:etiology
C507205:2-chloro-N-((S)-phenyl((2S)-piperidin-2-yl)methyl)-3-trifluoromethyl benzamide; D001549:Benzamides; D050487:Glycine Plasma Membrane Transport Proteins; D010880:Piperidines; C493268:SLC6A9 protein, human; D018698:Glutamic Acid; D005998:Glycine