The pharmacology of dobutamine.
Dobutamine is a sympathomimetic amine that was designed as an inotropic agent for use in congestive heart failure. Clinically, dobutamine increases cardiac output by selectively augmenting stroke volume, and this is associated with a decrease in total peripheral vascular resistance that is mediated, in part, by reflex withdrawal of sympathetic tone to the vasculature. This hemodynamic profile of dobutamine makes the drug of value in the management of low output cardiac failure. The inotropic activity of dobutamine has previously been attributed to selective stimulation of myocardial beta 1-adrenoceptors. However, recent studies from a number of laboratories indicate that the mechanism of action of dobutamine is substantially more complex. Dobutamine has the capacity to stimulate beta 1-, beta 2-, and alpha 1-adrenoceptors in the cardiovascular system at doses that approximate those used clinically. It has recently been suggested that the inotropic activity of dobutamine results from combined beta 1- and alpha 1-adrenoceptor stimulation in the myocardium, and that this activity could explain, at least in part, the inotropic selectivity of the compound. Furthermore, in the vasculature, the beta 2-adrenoceptor-mediated vasodilatory effect of dobutamine is exactly offset by the alpha 1-adrenoceptor-mediated vasoconstrictor activity, such that net changes in blood pressure are minimal following the administration of dobutamine. It is concluded, therefore, that the hemodynamic profile of dobutamine in patients with congestive heart failure is derived from a unique and complex series of interactions with alpha- and beta-adrenoceptors in the cardiovascular system.
Ruffolo
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Department of Pharmacology, Smith Kline & French Laboratories, Swedeland, Pennsylvania 19479.
D004280:Dobutamine / Q000494:pharmacology*; D006333:Heart Failure / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D009200:Myocardial Contraction / Q000187:drug effects
D004280:Dobutamine