D-serine antagonized phencyclidine- and MK-801-induced stereotyped behavior and ataxia.
D-Serine, a selective agonist at the strychnine-insensitive glycine binding site, antagonized PCP-induction of stereotyped behavior and ataxia in a dose-dependent manner. At intraventricular doses of 0.1, 0.5 and 1 mumol/rat, D-serine significantly attenuated PCP-induction of stereotyped behavior in rats. Only doses of 0.5 and 1.0 mumol/rat of D-serine antagonized PCP-induction of ataxia. D-Serine (0.5 mumol/rat) also antagonized MK-801 induced stereotyped behavior and ataxia. These results suggest that agonists at the strychnine-insensitive glycine site may be clinically useful as a novel class of atypical antipsychotic agents.
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CNS Diseases Research, G. D. Searle and Company, St. Louis, MO 63198.
D000818:Animals; D001259:Ataxia / Q000139:chemically induced* / Q000503:physiopathology; D003986:Dibenzocycloheptenes / Q000037:antagonists & inhibitors*; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D007276:Injections, Intraventricular; D008297:Male; D010622:Phencyclidine / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012694:Serine / Q000494:pharmacology*; D013239:Stereotyped Behavior / Q000187:drug effects*
D003986:Dibenzocycloheptenes; D012694:Serine; D016291:Dizocilpine Maleate; D010622:Phencyclidine