NEW PUTATIVE SELECTIVE AGONISTS AT THE D-1 DOPAMINE RECEPTOR - BEHAVIORAL AND NEUROCHEMICAL COMPARISON OF CY-208-243 WITH SK-AND-F-101384 AND SK-AND-F-103243

Three putative D-1 agonists with nonbenzazepine structures were compared with the prototype benzazepine D-1 partial agonist SK&F 38393 for their behavioural effects in the intact adult rat, and for their relative affinities for D-1 and D-2 dopamine receptors in vitro. SK&F 103243, a restricted conformation analogue of SK&F 38393, and SK&F 101384 (8-Cl-ADTN) showed low affinity for D-1 and D-2 receptors in vitro binding studies, and failed to induce any behavioural effects on peripheral administration. CY 208-243, an indolophenanthridine derivative, showed appreciable affinity not only for D-1 receptors, but also for D-2 receptors, while in behavioural studies it showed some of the characteristics of a partial D-1 dopamine receptor agonist; thus, it failed to promote stereotyped behaviour, but induced episodes of intense grooming which were sensitive to blockade by the D-1 antagonist SCH 23390. No such effect was induced by the selective D-2 agonist RU 24213. CY 208-243 is the first nonbenzazepine which shows some of the properties of a D-1 agonist in the intact adult animal. However, the differences between its in vitro binding characteristics and its functional properties remain enigmatic. © 1990.