Meltzer H Y
Laboratory of Biological Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio.
J Clin Psychiatry. 1994 Sep;55 Suppl B:47-52.
Clozapine has multiple clinical advantages that differentiate it from typical neuroleptics but that it may share with other novel antipsychotic drugs such as risperidone and olanzapine. There may be more than one pharmacologic feature that contributes to its advantages in improving psychopathology, cognition, affect, tardive dyskinesia, etc. Clozapine has < 10 nM affinity for the serotonin (5-HT)2A, 5-HT2C, 5-HT6, 5-HT7, D4, m1, and alpha 1-adrenergic receptor but weak affinity for the D2 receptor. Current evidence suggests the 5-HT2A and D4 receptor antagonist properties of clozapine, together with its weak D2 blocking properties, contribute the most to its advantages and should be sought in drug development programs. However, the other effects of clozapine may also be contributory. Clozapine is effective in a variety of conditions and at a range of plasma levels. The effects that are important in various indications may differ.
氯氮平具有多种临床优势，使其有别于传统抗精神病药物，但它可能与其他新型抗精神病药物（如利培酮和奥氮平）有共同之处。可能有不止一种药理特性促成了其在改善精神病理学、认知、情感、迟发性运动障碍等方面的优势。氯氮平对5-羟色胺（5-HT）2A、5-HT2C、5-HT6、5-HT7、D4、m1和α1-肾上腺素能受体的亲和力小于10 nM，但对D2受体的亲和力较弱。目前的证据表明，氯氮平的5-HT2A和D4受体拮抗特性，连同其较弱的D2阻断特性，对其优势的贡献最大，应在药物研发项目中予以探寻。然而，氯氮平的其他作用也可能有促成作用。氯氮平在多种情况下以及一系列血浆浓度水平下均有效。在各种适应症中起重要作用的效应可能有所不同。
