Comparison of the effects of various typical and atypical antipsychotic drugs on the suppressant action of 2-methylserotonin on medial prefrontal cortical cells in the rat

✍ Scribed by Charles R. Ashby Jr.; Yoshio Minabe; Emmeline Edwards; Rex Y. Wang

• Publisher: John Wiley and Sons
• Year: 1991
• Tongue: English
• Weight: 767 KB
• Volume: 8
• Category: Article
• ISSN: 0887-4476
• DOI: 10.1002/syn.890080302

✦ Synopsis

In this study, we report the effects of various typical and atypical antipsychotic drugs (APDs) on the suppressant action of microiontophoretically applied 2-methylserotonin (2-Me-5HT, a 5-HT3 agonist) on medial prefrontal cortical (mPFc) cells. The microiontophoresis of 2-Me-5HT (10-80 nA) produced a current-dependent suppression of mPFc cells' firing, and this effect was blocked by various 5-HT3 antagonists. The microiontophoresis of the atypical APDs clozapine and a structurally related compound, RMI 81,582, mimicked the action of the 5-HT3 antagonists. In addition, the intravenous administration of clozapine and RMI 81,582 antagonized the suppressant action produced by the iontophoretic application of 2-Me-5HT on mPFc cells. However, the suppressant action of 2-Me-5HT was not blocked by the typical APDs haloperidol and chlorpromazine.

The putative atypical APDs risperidone, setoperone, CL 77328, SCH 23390, CGS 10746B, l-sulpiride, and thioridazine were ineffective in antagonizing 2-Me-5HTs action. Overall, our results suggest that the majority of putative atypical APDs do not interact with 5-HT3 binding sites in the brain. Whether the interaction of clozapine and RMI 81,582 with 5-HT3 sites is correlated with their therapeutic efficacy or lower potential to induce neurological side effects remains to be determined.