Labetalol binding to specific alpha- and beta-adrenergic sites in vitro and its antagonism of adrenergic responses in vivo.

Labetalol was found to compete with ³H]dihydroergocryptine for specific alpha-adrenergic binding sites in rabbit uterine membrane preparations. Based on IC50 values from binding-competition curves, labetalol had 536 times lower affinity for alpha-sites than phentolamine. Labetalol competed with ³H]dihydroalprenolol for specific beta-adrenergic binding sites in guinea pig heart and lung membranes. The drug had 53 times lower affinity for the heart beta-sites than propranolol, and was significantly less potent than propranolol in inhibiting stimulation of cardiac adenylate cyclase by 10^?5 m isoproterenol. Labetalol had 19 times greater binding affinity for beta binding sites in heart membranes than alpha binding sites in uterine membranes. In vivo studies in anesthetized dogs indicate that blockade of beta adrenergic responses predominates at lower dose of labetalol and that blockade of alpha responses was observed when the dose was increased by a factor of 10. These data are consistent with the hypothesis that labetalol antagonizes both alpha and beta adrenoceptors, and that labetalol is a more potent antagonist at beta than alpha-adrenergic sites.