ALPHA AND BETA-ADRENERGIC EFFECTS OF THE STEREOISOMERS OF DOBUTAMINE

  • 1 January 1981
    • journal article
    • research article
    • Vol. 219  (2) , 447-452
Abstract
Dobutamine and its stereoisomers were evaluated for .alpha. and .beta. adrenergic activities in vitro. The racemate and the (-)-isomer were 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. 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.