The effect of typical and atypical antipsychotic drugs on the stimulation of phosphoinositide hydrolysis produced by the 5-HT3 receptor agonist 2-methyl-serotonin.
The atypical antipsychotic drug clozapine (CLOZ) and a structurally related compound RMI 81,582 (RMI) dose-dependently inhibited the stimulation of phosphoinositide hydrolysis induced by the 5-HT3 receptor agonist 2-methyl-serotonin in the rat fronto-cingulate and entorhinal cortices. The antagonism of 2-methyl-serotonin's stimulation of phosphoinositide hydrolysis by CLOZ and RMI was comparable to that observed with 5-HT3 antagonists such as granisetron, ondansetron, ICS 205-930 and zacopride. By contrast, the typical antipsychotic drugs haloperidol (HAL) and chlorpromazine (CPZ) did not antagonize the stimulation of phosphoinositide hydrolysis induced by 2-methyl-serotonin. The 5-HT3 receptor antagonizing effect of CLOZ and RMI may contribute to the 'atypical' pharmacological profile of these antipsychotic drugs.
Edwards
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Department of Psychiatry and Behavioral Science, State University of New York, Stony Brook 11794-8101.
Ashby
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Wang
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D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002746:Chlorpromazine / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D003984:Dibenzazepines / Q000494:pharmacology*; D006868:Hydrolysis; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology
D014150:Antipsychotic Agents; D003984:Dibenzazepines; D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D011985:Receptors, Serotonin; D012701:Serotonin; C023864:RMI 81,582; D007294:Inositol; C045918:2-methyl-5-HT; D003024:Clozapine; D002746:Chlorpromazine