Glycyldodecylamide, a phencyclidine behavioral antagonist, blocks cortical glycine uptake: implications for schizophrenia and substance abuse.
N-Methyl-D-aspartate (NMDA) antagonists induce psychotomimetic effects in humans that closely resemble negative and cognitive symptoms of schizophrenia. NMDA agonists, in contrast, may significantly ameliorate such symptoms. In rodents, phencyclidine (PCP) and other NMDA antagonists induce a hyperlocomotory syndrome that is reversed by NMDA agonists. The present study investigates the mechanism of action of glycyldodecylamide (GDA), a drug that is 80-fold more potent than glycine in reversing PCP-induced hyperactivity in rodents. At concentrations relevant to its behavioral actions, GDA significantly inhibits forebrain glycine uptake, indicating that glycine uptake inhibition may provide effective treatment for PCP psychosis and PCP psychosis-like symptoms of schizophrenia.
Javitt
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Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10692, USA. javitt@iris.rfmh.org
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D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D005998:Glycine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D010622:Phencyclidine / Q000037:antagonists & inhibitors*; D000644:Quaternary Ammonium Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D017478:Receptors, Phencyclidine / Q000378:metabolism; D012559:Schizophrenia / Q000188:drug therapy; D019966:Substance-Related Disorders / Q000188:drug therapy; D013574:Synaptosomes / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D018691:Excitatory Amino Acid Antagonists; D000644:Quaternary Ammonium Compounds; D016194:Receptors, N-Methyl-D-Aspartate; D017478:Receptors, Phencyclidine; C109520:glycyldodecylamide; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016291:Dizocilpine Maleate; D010622:Phencyclidine; D005998:Glycine