Tice M A, Hashemi T, Taylor L A, Duffy R A, McQuade R D
Schering-Plough Research Institute, Kenilworth NJ 07033.
Pharmacol Biochem Behav. 1994 Nov;49(3):567-71. doi: 10.1016/0091-3057(94)90070-1.
Characterization studies were conducted on the five cloned dopamine receptor subtypes (D1-D5) using the novel D1-selective antagonist, SCH 39166, as well as other related benzazepines and dopaminergic agents. The results demonstrate that SCH 39166 exhibits saturable, high-affinity binding to the D1 and D5 receptors, but binds with low affinity to the D2, D3, and D4 receptors. In contrast, the D2 antagonist haloperidol showed low affinity for the "D1-like" receptors and high affinity for the "D2-like" receptors. A series of agonists was also evaluated and the D5 receptor subtype displayed a two-site fit for the endogenous agonist dopamine, as well as for the agonist apomorphine. Differences in agonist binding among the D1-like receptors reflect the importance of the nonconserved amino acid substitutions.
使用新型D1选择性拮抗剂SCH 39166以及其他相关苯并氮杂卓类和多巴胺能药物，对五种克隆的多巴胺受体亚型（D1 - D5）进行了特性研究。结果表明，SCH 39166对D1和D5受体表现出可饱和的高亲和力结合，但对D2、D3和D4受体的结合亲和力较低。相比之下，D2拮抗剂氟哌啶醇对“D1样”受体亲和力低，对“D2样”受体亲和力高。还评估了一系列激动剂，D5受体亚型对内源性激动剂多巴胺以及激动剂阿扑吗啡呈现出双位点拟合。D1样受体之间激动剂结合的差异反映了非保守氨基酸取代的重要性。
