The effect of typical and atypical antipsychotic drugs on the stimulation of phosphoinositide hydrolysis produced by the 5-HT3 receptor agonist 2-methyl-serotonin

Brain Res. 1991 Apr 5;545(1-2):276-8. doi: 10.1016/0006-8993(91)91296-d.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antipsychotic Agents / pharmacology*
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism*
  • Chlorpromazine / pharmacology*
  • Clozapine / pharmacology*
  • Dibenzazepines / pharmacology*
  • Hydrolysis
  • In Vitro Techniques
  • Inositol / metabolism
  • Inositol Phosphates / metabolism*
  • Male
  • Phosphatidylinositols / metabolism*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Serotonin / analogs & derivatives*
  • Serotonin / pharmacology

Substances

  • Antipsychotic Agents
  • Dibenzazepines
  • Inositol Phosphates
  • Phosphatidylinositols
  • Receptors, Serotonin
  • Serotonin
  • RMI 81,582
  • Inositol
  • 2-methyl-5-HT
  • Clozapine
  • Chlorpromazine