Effects of carvedilol on adrenergic receptor pharmacology in human ventricular myocardium and lymphocytes.

Carvedilol, a new β-blocker with vasodilating properties due to α1-blockade, was investigated in preparations of human ventricular myocardium. Carvedilol demonstrated a high affinity and is a slightly β1-selective competitive β-blocking agent, with a KD for β1-receptors of approximately 4–5 nM and a mild selectivity for β1 vs. β2 receptors of 6- to 39-fold, depending on the method employed to assess subtype potency. In addition, carvedilol was also a potent α1-blocking agent, with a β1:α1 blocking relative potency of 1.7-fold. In human lymphocytes containing β2-receptors and in human myocardial membranes containing both β1- and β2-receptors carvedilol exhibited the unique property of guanine nucleotide modulatable binding. Despite this, no intrinsic sympathomimetic activity of carvedilol was detected in preparations of isolated human heart or in myocardial membranes. Vasodilation related to α1-blockade and the lack of intrinsic activity should translate into improved tolerability and good efficacy in the treatment of heart failure.