Pharmacological characteristics of perospirone hydrochloride, a novel antipsychotic agent.

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  • OHNO Yukihiro
    Discovery Laboratory I, Research Center, Sumitomo Pharmaceuticals Co., Ltd.

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  • 新規抗精神病薬　塩酸ペロスピロンの薬理学的特性
  • シンキ コウセイシンビョウヤク エンサン ペロスピロン ノ ヤクリガクテキ トクセイ

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Abstract

It is now known that the blockade of 5-HT2 receptors can ameliorate the negative symptoms of schizophrenia and extrapyramidal side effects (EPS) associated with antipsychoitc treatments. Perospirone hydrochloride (perospirone), which was identified as a novel serotonin-dopamine antagonist (SDA)-type antipsychotic agent in 1987 by Sumitomo Pharmaceuticals, possesses high affinities both for dopamine 5-HT2 and D2 receptors. Perospirone, like conventional antipsychotics, significantly inhibited various behaviors induced by dopaminergic hyperactivation. Perospirone also produced a significant improvement in animal models of the negative symptoms and mood disorders, where the conventional antipsychotics were unaffected. In addition, perospirone was weaker than the conventional antipsychotics (e.g., haloperidol) in inducing EPS signs (e.g., catalepsy and bradykinesia), suggesting that the drug has an atypical antipsychotic property. A recent double-blind study with schizophrenia patients demonstrated that perospirone was comparative with haloperidol in improving the positive symptoms, but was significantly superior to haloperidol against the negative symptoms. Furthermore, the extrapyramidal score in patients with perospirone treatment was lower that those with haloperidol treatment. These findings suggested that perospirone acts as an antagonist both for 5-HT2 and D2 receptors and has broader clinical efficacy and lower EPS liability than haloperidol in schizophrenia treatment.

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