PMID: 9437764Aug 1, 1997Paper

Potential role of 5-HT2 and D2 receptor interaction in the atypical antipsychotic action of the novel succimide derivative, perospirone

Polish Journal of Pharmacology
Y OhnoM Nakamura

Abstract

The pharmacological profile of the novel serotonin-dopamine antagonists (SDA)-type antipsychotic, perospirone, was compared with other SDA and typical antipsychotics, and a potential role of 5-HT2 and D2 receptor interaction in the atypical antipsychotic property of SDA was discussed based on the findings with selective 5-HT2 antagonists. Our study revealed that perospirone, like other SDA, differed from the typical antipsychotics by exhibiting 1) putative anxiolytic and/or antidepressant actions in some animal models (e.g., conditioned fear stress-induced freezing model and rat social interaction), 2) reduced extrapyramidal side effects (EPS) liability (catalepsy and bradykinesia induction), 3) weaker blocking actions at striatal D2 receptors as revealed by c-fos expression and dopamine turnover and 4) lower propensity to induce supersensitivity of dopamine receptors after repeated treatments (e.g., dopamine agonist-induced stereotyped behavior and vacuous chewing movement). The 5-HT2 antagonists mimicked the action of SDA antipsychotics in the animal models of mood disorder. In addition, combined treatments of 5-HT2 antagonists with typical antipsychotic could attenuate EPS induction and striatal c-fos expression associated w...Continue Reading

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