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Specificity of the dopamine sensitive adenylate cyclase for anti psychotic antagonists


Life Sciences 19(6): 927-934
Specificity of the dopamine sensitive adenylate cyclase for anti psychotic antagonists
Chlorpromazine, haloperidol and clozapine are approximately equipotent in antagonizing dopamine sensitive adenylate cyclase activity in homogenates of rat brain striatum. The antagonism appeared to occur at a structurally specific dopamine site, as inhibition by a series of chlorpromazine analogues of similar hydrophobicity exhibited a structural specificity similar to that found for their neuroleptic and cataleptic activities. Sulpiride, a dopamine antagonist with antipsychotic activity, and metochlopramide, a structurally related central dopamine antagonist, failed to inhibit the dopamine sensitive adenylate cyclase. Pretreatment of rats with haloperidol (3 mg/kg per day) for 6 or 28 days did not induce a supersensitive response of the adenylate cyclase to stimulation by dopamine or apomorphine or inhibition by clozapine. The dopamine sensitive adenylate cyclase may not be the site of action of all antipsychotic agents.


Accession: 006459034

PMID: 966971



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