RECEPTOR PHARMACOLOGY OF CARVEDILOL IN THE HUMAN HEART

The beta-blocker and vasodilator carvedilol was examined in preparations of human ventricular myocardium. Carvedilol is a high-affinity, slightly beta-1-selective competitive beta-blocking agent, with a K(D) for beta-1-receptors of approximately 4-5 nM and a selectivity of sixfold to 39-fold for beta-1-receptors rather than beta-2-receptors, depending on the method used to assess subtype potency. Carvedilol also is a potent alpha-1-blocking agent, with a beta-1:alpha-1-blocking relative potency of 1.7-fold. In human lymphocytes containing beta-2-receptors and human myocardial membranes containing both beta-1- and beta-2-receptors, carvedilol exhibited the unique property of guanine nucleotide-modulatable binding. This is a property shared with bucindolol, another beta-blocker and vasodilator that is structurally similar to carvedilol. Despite the presence of guanine nucleotide-modulatable binding, no intrinsic activity of carvedilol was detected in preparations of isolated human heart or in myocardial membranes.