[Glycine therapy of schizophrenia; its rationale and a review of clinical trials].
A major ground of dopamine hypothesis of schizophrenia is that all antipsychotics share dopamine D2 antagonistic activity. However, they are less effective in ameliorating the negative symptoms of schizophrenia. Recently, glutamate hypothesis of schizophrenia has been developed from the observation that phencyclidine, an NMDA receptor antagonist, induces a psychotic state closely resembling schizophrenia in normal individuals. Because glycine potentiates NMDA receptor activity, it has been tried as an adjunct to conventional antipsychotics. Most trials demonstrated a moderate improvement in negative symptoms. In this review we discussed the clinical usefulness of glycine therapy. First we described glutamate hypothesis of schizophrenia as a theoretical basis of glycine therapy. Then we reviewed clinical trials of glycine or other glycinergic agents (glycine receptor partial agonist, D-cycloserine, or the glycine prodrug milacemide). Although long-term side effects of glycine administration have not been fully investigated, glycine therapy could be a potential therapeutic tool for the negative symptoms of schizophrenia.
Semba
J
J
University of the Air, Division of Health Sciences, Chiba, Japan.
D000081:Acetamides / Q000627:therapeutic use; D000409:Alanine / Q000494:pharmacology / Q000627:therapeutic use; D026921:Amino Acid Transport Systems, Neutral; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D003523:Cycloserine / Q000627:therapeutic use; D018698:Glutamic Acid / Q000502:physiology; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use*; D050487:Glycine Plasma Membrane Transport Proteins; D006801:Humans; D011355:Prodrugs / Q000627:therapeutic use; D018009:Receptors, Glycine / Q000819:agonists; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists; D012559:Schizophrenia / Q000188:drug therapy* / Q000209:etiology; D012694:Serine / Q000494:pharmacology / Q000627:therapeutic use
D000081:Acetamides; D026921:Amino Acid Transport Systems, Neutral; D002352:Carrier Proteins; D050487:Glycine Plasma Membrane Transport Proteins; D011355:Prodrugs; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; C109520:glycyldodecylamide; C039332:milacemide; D018698:Glutamic Acid; D012694:Serine; D003523:Cycloserine; D000409:Alanine; D005998:Glycine