Roth B L, Craigo S C, Choudhary M S, Uluer A, Monsma F J, Shen Y, Meltzer H Y, Sibley D R
Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, Ohio.
J Pharmacol Exp Ther. 1994 Mar;268(3):1403-10.
The authors examined the affinities of 36 typical and atypical antipsychotic agents for the cloned rat 5-hydroxytryptamine-6 (5-HT6) and rat 5-hydroxytryptamine-7 (5-HT7) receptors in transiently expressed COS-7 cells (5-HT7) or stably transfected HEK-293 cells (5-HT6 receptors). Clozapine and several related atypical antipsychotic agents (rilapine, olanzepine, tiospirone, fluperlapine, clorotepine and zotepine) had high affinities for the newly discovered 5-HT6 receptor (Kis < 20 nM). The 5-HT7 receptor bound clozapine, rilapine, fluperlapine, clorotepine, zotepine and risperidone but not tiospirone and olanzepine, with affinities less than 15 nM. In addition, several typical antipsychotic agents (chloroprothixene, chlorpromazine, clothiapine and fluphenazine) had high affinities for both the 5-HT6 and 5-HT7 receptors. Pimozide, a diphenylbutylpiperidine, had the highest affinity of all the typical antipsychotic agents tested for the 5-HT7 receptor (Ki = 0.5 nM). Three putative atypical antipsychotic agents melperone, amperozide and MDL 100907 did not bind with high affinities to either the 5-HT6 or 5-HT7 receptors (Kis > 50 nM). Several dopamine-selective antipsychotic agents (raclopride, rimcazole and penfluridol) had essentially no affinity for either the 5-HT6 or 5-HT7 receptors (Ki values > 5000 nM).(ABSTRACT TRUNCATED AT 250 WORDS)
作者检测了36种典型和非典型抗精神病药物对瞬时表达的COS - 7细胞（5 - HT7受体）或稳定转染的HEK - 293细胞（5 - HT6受体）中克隆的大鼠5 - 羟色胺 - 6（5 - HT6）和大鼠5 - 羟色胺 - 7（5 - HT7）受体的亲和力。氯氮平和几种相关的非典型抗精神病药物（利拉平、奥氮平、替螺酮、氟哌拉平、氯替平及佐替平）对新发现的5 - HT6受体具有高亲和力（抑制常数<20 nM）。5 - HT7受体与氯氮平、利拉平、氟哌拉平、氯替平、佐替平和利培酮结合，但不与替螺酮和奥氮平结合，其亲和力小于15 nM。此外，几种典型抗精神病药物（氯普噻吨、氯丙嗪、氯噻平及氟奋乃静）对5 - HT6和5 - HT7受体均具有高亲和力。匹莫齐特，一种二苯基丁基哌啶，在所测试的所有典型抗精神病药物中对5 - HT7受体具有最高亲和力（抑制常数=0.5 nM）。三种假定的非典型抗精神病药物美哌隆、氨哌齐特和MDL 100907对5 - HT6或5 - HT7受体均无高亲和力（抑制常数>50 nM）。几种多巴胺选择性抗精神病药物（雷氯必利、利木唑及五氟利多）对5 - HT6或5 - HT7受体基本无亲和力（抑制常数>5000 nM）。（摘要截短于250字）
