【摘要】 目的:研究四氢原小檗碱类（THPB）对脑内多巴胺受体D₁和D₂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D₁受体以R_H和R_L双位点结合,它们在C₂和C₉或C₂和C₁₀位有两个羟基,另外11个THPB与D₁受体以单位点结合.对于D₂受体,11个被检测的化合物均以单位点结合,其中,在C₂位有羟基的THPB亲和力最强.结论:在C₂和C₉或C₂和C₁₀位有双羟基的THPB具有D₁受体激动剂的内在活性,其它THPB则无此活性.11个THPB均为D₂受体拮抗剂.更多还原

【Abstract】 AIM: To study the characteristics of tetrahydroprotoberberines (THPB) on dopamine D1 and D2 receptors and elucidate their structure-activity relationship. METHODS: Radioligand assay in vitro with a two-site model program analysis. RESULTS: Four THPB with two hydroxyl groups on C2 and C9 or C2 and C10 exhibited R11 and RL two binding sites to D1 receptors and guanosine triphosphate regulated the RH binding site of SPD and THPB-132A in competition assay, while eleven THPB including nonhydroxy-THPB, monohydroxy-THPB, and THPB with two hydroxyl groups attaching to C3 and C10 showed one binding site to D1 receptors under the same conditions. However, the tested eleven THPB all manifested one binding site to D2 receptors in competition assay, and the 2-hydroxy-THPB had the most potent affinity for D2 receptors. CONCLUSION: Dihydroxy-THPB with two hydroxyl groups attaching to C2 and C9 or C2 and C10 possess the intrinsic activity of agonist to D1 receptors, while the other THPB do not. The tested eleven THPB all are the antagonists of D2 receptors.更多还原