Alpha and beta adrenergic effects of the stereoisomers of dobutamine.

Dobutamine and its stereoisomers were evaluated for alpha and beta adrenergic activities in vitro. The racemate and the (--)-isomer were found to be potent partial agonists of alpha adrenergic receptors in rat aorta. The (+)-isomer lacked alpha agonist activity. The affinities of (+/-)-, (+)- and (--)-dobutamine for the alpha adrenergic receptor were high (--log KB values of 7.01, 7.02 and 7.07, respectively) and not significantly different from one another. These data indicate that (+)- and (--)- dobutamine bind equally to the alpha adrenergic receptor, however, subsequent to binding, only the (--)-isomer is capable of activating the receptor and eliciting an alpha adrenergic response. The (+)-isomer, which has the same affinity as the (--)-isomer but which lacks agonist activity, is a potent competitive alpha blocker. Both stereoisomers of dobutamine were agonists of beta adrenergic receptors of cat papillary muscle and right atria. In contrast to the alpha adrenergic effects, the more potent isomer at the beta adrenergic receptor was (+)- dobutamine. The isomeric activity ratio for the stereoisomers of dobutamine was approximately 1 log unit in favor of the (+)-isomer with respect to both inotropic and chronotropic responses. Dose-response curves to the racemate were always situated between the stereoisomers, approximately 2-fold to the right of (+)-dobutamine. These results indicate that the stereochemical requirements of alpha and beta adrenergic receptors are opposite for the stereoisomers of dobutamine with the alpha receptor favoring the (--)-isomer and the beta receptor favoring the (+)-isomer.