替米哌隆对3H-螺哌啶醇与大鼠纹状体多巴胺受体结合的影响。

Effect of timiperone on 3H-spiroperidol binding to rat striatal dopamine receptors.

作者信息

Tachizawa H, Sudo K, Sano M

出版信息

Eur J Pharmacol. 1979 Nov 16;59(3-4):245-51. doi: 10.1016/0014-2999(79)90287-5.

Abstract

The effects of timiperone, its metabolites and related compounds on specific 3H-spiroperidol binding to dopamine receptors in the rat corpus striatum were studied to clarify the affinity of timiperone, a new butyrophenone, for the receptors and whether timiperone itself was active in vivo. Timiperone had an approx. 0.6, 5 and 30 times greater affinity for the receptors than did spiroperidol, haloperidol and chlorpromazine, respectively. This affinity was observed specifically for antipsychotic drugs but not for diazepam and trihexyphenidyl. Timiperone metabolites had little or no affinity for the receptors. Radioreceptor assay values agreed well with the radiochemical assay for timiperone in the plasma and brain of rats after i.v. injection of the 14C-labeled drug. Thus, it is conceivable that timiperone itself exerts its potent antipsychotic activity by blockade of cerebral dopamine receptors.

摘要

研究了替米哌隆及其代谢产物和相关化合物对大鼠纹状体中特异性3H-螺哌啶醇与多巴胺受体结合的影响，以阐明新型丁酰苯类药物替米哌隆对受体的亲和力以及替米哌隆本身在体内是否具有活性。替米哌隆对受体的亲和力分别比螺哌啶醇、氟哌啶醇和氯丙嗪约高0.6倍、5倍和30倍。这种亲和力在抗精神病药物中具有特异性，而在地西泮和苯海索中则未观察到。替米哌隆代谢产物对受体几乎没有或没有亲和力。放射性受体分析值与静脉注射14C标记药物后大鼠血浆和脑中替米哌隆的放射化学分析结果非常吻合。因此，可以设想替米哌隆本身通过阻断脑多巴胺受体发挥其强效抗精神病活性。