Dopamine receptor stimulating and alpha adrenoceptor blocking actions of trans (CS-265) and cis (CS-263) isomers of nonhydroxylated N-propyl octahydrobenzo[F]quinoline

M Ilhan, JP Long and JG Cannon

Experiments were designed to determine the dopaminergic and alpha adrenergic receptors involvement of cis (CS-263) and trans (CS-265) isomers of nonhydroxylated N-propyl octahydrobenzo[f]quinoline. Both compounds caused competitive blockade of presynaptic alpha-2 adrenoceptors of guinea-pig ileum and rat vas deferens. Postsynaptic alpha-1 adrenoceptors of rabbit aorta was inhibited. In the guinea-pig ileum, these compounds were found to be as active as yohimbine. In the rabbit aorta, they were weaker antagonists of phenylephrine than prazosin. CS-compounds reversed epinephrine-induced pressor responses and inhibited reflex hypertensive responses to stimulation of the central stump of sciatic nerve in anesthetized cats. Only CS-265 inhibited reflex tachycardia of sciatic nerve stimulation. In isolated cat right atria, CS-265 inhibited stimulation-induced tachycardic response through stimulation of presynaptic dopamine receptors in contrast to CS-263 that produced potentiation of stimulation-induced tachycardia. The results suggest that CS-265 is an unusual compound having dopamine receptor stimulating activity and alpha adrenoceptor blocking properties. These divergent properties provide direct evidence that presynaptic alpha-2 adrenoceptors and dopamine-receptors are different entities on the sympathetic nerve terminal.

Volume 231, Issue 2, pp. 361-366, 11/01/1984
Copyright © 1984 by American Society for Pharmacology and Experimental Therapeutics