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.
Department of Psychiatry and Behavioral Science, State University of New York, Stony Brook 11794-8101.
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E
Edwards
C R
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Ashby
R Y
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Wang
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