四氢原小檗碱类对小牛纹状体D_1和D_2多巴胺受体结合的特性(英文)

• 作 者: 郭翔 王黎明 刘健 金国章
• 机 构: 中国科学院上海药物研究所,中国科学院上海药物研究所,中国科学院上海药物研究所,中国科学院上海药物研究所 上海 200031 中国,上海 200031 中国,上海 200031 中国,上海 200031
• 出 处: Acta Pharmacologica Sinica
• 发表日期: 1997年03期
• 关键词: 纹状体 D_2 D_1 多巴胺受体 螺哌隆 鸟苷三磷酸 千金藤立定 放射配位体测定 12-氯代斯阔任 Sch-23390

目的:研究四氢原小檗碱类(THPB)对脑内多巴胺受体D_1和D_2亚型的结合特性,并阐明它们之间的构效关系.方法:放射配位体测定结合双位点模型分析.结果:4个THPB与D_1受体以R_H和R_L双位点结合,它们在C_2和C_9或C_2和C_(10)位有两个羟基,另外11个THPB与D_1受体以单位点结合.对于D_2受体,11个被检测的化合物均以单位点结合,其中,在C_2位有羟基的THPB亲和力最强.结论:在C_2和C_9或C_2和C_(10)位有双羟基的THPB具有D_1受体激动剂的内在活性,其它THPB则无此活性.11个THPB均为D_2受体拮抗剂.

OBJECTIVE: To study the binding properties of tetrahydroprotoberberines (THPB) to dopamine D_1 and D_2 subtypes in brain and to elucidate the structure-activity relationship between them.Methods: Radioligand assay combined with the two-site model RESULTS: Four THPB and D_1 receptors were bound by R_H and R_L double sites, they had two hydroxyl groups at C_2 and C_9 or C_2 and C_ (10) sites, and another 11 THPBs were bound to D_1 receptor at a single site For the D_2 receptor, 11 of the tested compounds were bound at a single site, of which, THPB with the hydroxyl group at C_2 had the strongest affinity.Conclusion: THPB with two hydroxyl groups at C_2, C_9 or C_2 and C_ (10) There is intrinsic activity of D_1 receptor agonist, while no activity of other THPBs. All 11 THPBs are D_2 receptor antagonists.