A novel antipsychotic, perospirone, has antiserotonergic and antidopaminergic effects in human brain: findings from neuroendocrine challenge tests

Rationale: Perospirone is a new antipsychotic drug in which dopamine D-2 antagonist and serotonin 5-HT2 antagonist effects have been found in animal studies. It was developed by a Japanese pharmaceutical company and launched in 2001. Perospirone's receptor binding profile may resemble that of atypical antipsychotic drugs, but to date there has been no evidence relating to its receptor binding affinity in the human brain. Objective: The purpose of this study was to investigate the receptor binding profile of perospirone via neuroendocrine challenge tests. Methods: Twenty subjects (ten females and ten males) were tested on four occasions in a double-blind, cross-over design receiving: (a) placebo, (b) perospirone 4 mg, (c) paroxetine 20 mg, and (d) paroxetine 20 mg plus perospirone 4 mg, administered orally at 8.00 a.m. Plasma cortisol and prolactin levels were measured prior to administration and every hour for 6 h thereafter. In addition, psychological responses rated by visual analog scales and vital signs such as body temperature, pulse, and blood pressure were assessed in combination with blood sampling. Results: Perospirone 4 mg increased prolactin levels significantly higher than placebo, whereas paroxetine 20 mg plus perospirone 4 mg significantly attenuated cortisol responses induced by paroxetine 20 mg. Conclusions: The present findings suggest that perospirone has the characteristics of both D-2 and 5-HT2 antagonist in the human brain. Further PET studies in the human brain are required in order to directly investigate these effects.