Reversal of phencyclidine-induced hyperactivity by glycine and the glycine uptake inhibitor glycyldodecylamide.
Phencyclidine (PCP) induces a psychotic state that closely resembles schizophrenia. In preclinical studies, PCP has been shown to induce its unique behavioral effects by blocking excitatory neurotransmission mediated at the N-methyl-D-aspartate (NMDA) receptors, suggesting that agents which potentiate NMDA receptor-mediated neurotransmission might have clinically beneficial effects. The present study demonstrates that the NMDA co-agonist glycine inhibits rodent hyperactivity induced by PCP, but not amphetamine. Glycyldodecylamide, a compound that blocks neuronal glycine uptake and which may therefore increase intrasynaptic glycine levels, inhibits PCP-induced hyperactivity more potently than glycine. These results complement recent clinical studies with glycine and suggest that glycine-uptake inhibitors, as well as glycine, may be beneficial in the treatment of PCP-induced psychosis and schizophrenia.
Javitt
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DC
Nathan Kline Institute for Psychiatric Research, Orangeburg, New York 10962, USA.
Sershen
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H
Hashim
A
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Lajtha
A
A
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D010622:Phencyclidine / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; C109520:glycyldodecylamide; D000661:Amphetamine; D010622:Phencyclidine; D005998:Glycine