Roth B L, Ciaranello R D, Meltzer H Y
Nancy Pritzker Laboratory of Molecular and Developmental Neurobiology, Department of Psychiatry, Stanford University School of Medicine, California.
J Pharmacol Exp Ther. 1992 Mar;260(3):1361-5.
We determined the affinities of clozapine and 21 other typical and atypical antipsychotic agents for the cloned 5-hydroxytryptamine-1C (5-HT1C) receptor. For these studies, 5-HT1C receptors were transiently expressed in COS-7 cells using the vector pSVK3-5HT1C. We discovered that clozapine and several other putative typical and atypical antipsychotic agents (loxapine greater than tiosperone greater than SCH23390 greater than fluperlapine greater than rilapine greater than chlorpromazine) had relatively high affinities (7-30 nM) for the cloned 5-HT1C receptor. Other antipsychotic agents (risperidone greater than tenilapine greater than mesoridazine greater than thioridazine greater than cis-fluphenthixol) had intermediate affinities (30-100 nM), whereas many other antipsychotics (fluphenazine greater than spiperone greater than amperozide greater than melperone greater than thiothixene greater than haloperidol, metoclopramide, pimozide, domperidone, sulpiride) had low affinities (greater than 500 nM) for the cloned 5-HT1C receptor. The results indicate that although several putative atypical antipsychotic agents have high affinities for the cloned rat 5-HT1C receptor, the spectrum of drug binding does not correlate with the atypical nature of these compounds.
我们测定了氯氮平以及其他21种典型和非典型抗精神病药物对克隆的5-羟色胺-1C（5-HT1C）受体的亲和力。在这些研究中，使用载体pSVK3-5HT1C在COS-7细胞中瞬时表达5-HT1C受体。我们发现氯氮平以及其他几种假定的典型和非典型抗精神病药物（洛沙平大于替沃噻吨大于SCH23390大于氟哌拉平大于瑞立哌嗪大于氯丙嗪）对克隆的5-HT1C受体具有相对较高的亲和力（7 - 30 nM）。其他抗精神病药物（利培酮大于替尼拉平大于美索达嗪大于硫利达嗪大于顺式氟奋乃静）具有中等亲和力（30 - 100 nM），而许多其他抗精神病药物（氟奋乃静大于螺哌隆大于氨哌齐特大于美哌隆大于硫杂蒽酮大于氟哌啶醇、甲氧氯普胺、匹莫齐特、多潘立酮、舒必利）对克隆的5-HT1C受体具有低亲和力（大于500 nM）。结果表明，尽管几种假定的非典型抗精神病药物对克隆的大鼠5-HT1C受体具有高亲和力，但药物结合谱与这些化合物的非典型性质并不相关。
