Dopamine D1 and D2 receptor selectivities of phenyl-benzazepines in rhesus monkey striata

Several phenyl-benzazepine compounds, putatively selective dopanzine D-1 receptor agonists, have been used to study the effects of dopamine D-1 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 D-1-like and D-2-like receptors were assessed in rhesus monkey and, for comparison, rat striata. The compounds tested had higher affinity for D-1 than D-2 receptors in both species; however, their selectivity varied by up to three orders of magnitude. GTP (100 mu M) reduced agonist binding at the high-affinity state of the dopamine D-1 receptor, but the magnitude of the effect of CTP 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 D-1 dopamine receptor agonists. (C) 1998 Elsevier Science B.V. All rights reserved.