Pharmacology of Labetalol in Experimental Animals

Labetalol represents the culmination of an effort to enhance the antihypertensive efficacy and to improve the hemodynamic profile of beta-adrenoceptor blockers by incorporating an additional anti-hypertensive action, that is, alpha blockade, into its pharmacologic mechanism. Reviewed here are the major aspects of the animal pharmacology of labetalol. The compound blocks beta1 and beta2-adrenoceptors nonselectively. Its blockade of alpha receptors is selective and directed at the alpha1 subset. Labetalol also dilates blood vessels independently of these mechanisms. This action is mediated by activation of vascular beta2 adrenoceptors. Thus, labetalol acts as a partial agonist on vascular smooth muscle. However, it differs markedly from other beta blockers with intrinsic sympathomimetic activity in that its agonism is directed specifically at beta2 receptors. Labetalol lowers blood pressure in a variety of animal models of hypertension. Unlike pure beta blockers, the compound reduces peripheral vascular resistance. On the basis of this profile, it is proposed that labetalol lowers blood pressure in human subjects by three independent mechanisms: (1) beta blockade, (2) alpha blockade, and (3) direct vasodilatation.