(3aα,7aα)-2-[4-[4-(1,2-ベンゾイソチアゾール-3-イル)-1-ピペラジニル]ブチル]ヘキサヒドロ-1H-イソインドール-1,3(2H)-ジオン

説明Perospirone hydrochloride was launched in Japan as a new treatment of schizophrenia and other psychoses. This structurally-related analog of ziprasidone can be classically prepared by alkylation of 1-(3-benzisothiazolyl)-piperazine with the appropriate N- (chlorobutyl)-succinimide. As a result of an in vitro determination of its binding profile, perospirone demonstrated a high affinity for 5-HT2, 5-HT1A and D2 receptors as well as a significant but lower affinity for DI and al receptors. Interestingly, these differential effects on neurotransmitters with a high in vivo occupancy of 5-HT2A receptors with lower D2 occupancy seems to provide this new agent with a significantly lower propensity for the development of extrapyramidal symptoms (EPS) and tardive schizophrenia, the main sideeffects associated with classical antipsychotic therapy. Furthermore, perospirone exhibited anxiolytic-like effects in animal models. A long-term clinical trial (> 6 months) in a group of patients suffering from schizophrenia demonstrated the efficacy of perospirone over placebo for the treatment of the positive, negative and general symptoms of schizophrenia at doses of 12 mg to 96 mg t.i.d.