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Perospirone hydrochloride: the novel atypical antipsychotic agent with high affinities for 5-HT2, D2 and 5-HT1A receptors

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We reviewed the pharmacological properties of perospirone hydrochloride (perospirone), a novel atypical antipsychotic agent, and discussed the potential role of 5-HT2 and 5-HT1A receptors in its action for the treatment of schizophrenia. Perospirone shows potent 5-HT2 and D2 receptor blocking activities in various animal models in vivo. Unlike other serotonin and dopamine antagonists (SDA), such as risperidone and olanzapine, perospirone exhibits a high affinity for 5-HT1A receptors, and acts as a partial agonist. Perospirone has efficacies not only for classical animal models for schizophrenia, but also in the models of negative symptoms and mood disorders, where the typical antipsychotics were inactive. In addition, perospirone has a weaker propensity to induce extrapyramidal side effects, such as catalepsy and bradykinesia in rodents, compared with haloperidol and risperidone. Depressant actions of the central nervous system (e.g. potentiation of anesthesia and inhibition of motor coordination) and a lower propensity to induce orthostatic hypotension seemed to be low. Our studies revealed that serotonergic mechanisms of perospirone (i.e. 5-HT2 receptor and 5-HT1A receptor action) are involved in its atypical properties such as weaker propensities to induce extrapyramidal side-effects or improvement of mood disturbance. These findings suggest that perospirone is a new type of antipsychotic agent with a broad therapeutic spectrum and fewer side effects.


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