Weed M R, Woolverton W L, Paul I A
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Eur J Pharmacol. 1998 Nov 13;361(1):129-42. doi: 10.1016/s0014-2999(98)00669-4.
Several phenyl-benzazepine compounds, putatively selective dopamine D1 receptor agonists, have been used to study the effects of dopamine D1 receptor stimulation in rodents and nonhuman primates. However, the dopamine receptor selectivities of these compounds have not been established in nonhuman primates. Accordingly, the relative selectivities of six phenyl-benzazepines for dopamine D1-like and D2-like receptors were assessed in rhesus monkey and, for comparison, rat striata. The compounds tested had higher affinity for D1 than D2 receptors in both species; however, their selectivity varied by up to three orders of magnitude. GTP (100 microM) reduced agonist binding at the high-affinity state of the dopamine D1 receptor, but the magnitude of the effect of GTP did not reliably predict a compound's efficacy. Furthermore, a history of cocaine self-administration did not appear to influence dopamine receptor binding characteristics in the rhesus monkeys in this study. The present results will aid the comparison of dopamine receptor binding characteristics and behavioral effects of D1 dopamine receptor agonists.
几种被认为是选择性多巴胺D1受体激动剂的苯基苯并氮杂䓬化合物，已被用于研究多巴胺D1受体刺激对啮齿动物和非人类灵长类动物的影响。然而，这些化合物对多巴胺受体的选择性在非人类灵长类动物中尚未得到证实。因此，在恒河猴中评估了六种苯基苯并氮杂䓬对多巴胺D1样和D2样受体的相对选择性，并与大鼠纹状体进行比较。在两个物种中，所测试的化合物对D1受体的亲和力均高于对D2受体的亲和力；然而，它们的选择性差异高达三个数量级。GTP（100 microM）降低了多巴胺D1受体高亲和力状态下的激动剂结合，但GTP的作用幅度并不能可靠地预测化合物的效力。此外，在本研究中，可卡因自我给药史似乎并未影响恒河猴的多巴胺受体结合特性。目前的结果将有助于比较多巴胺受体结合特性以及D1多巴胺受体激动剂的行为效应。
