CLINICAL-PHARMACOLOGY OF VASODILATORY BETA-BLOCKING DRUGS

The clinical pharmacology of beta-adrenoceptor blockers is summarized. They have a variety of pharmacological actions on the beta-adrenoceptors. For example, propranolol is a nonselective beta-blocker with antagonist effects on both beta-1 and beta-2 receptors, atenolol is a selective beta-1-antagonist, and celiprolol is a selective beta-1-antagonist, partial beta-2-agonist. beta-1-Receptor blockade tends to reduce heart rate, cardiac output, and arterial pressure while increasing peripheral vascular resistance, whereas beta-2-receptor blockade tends to be disadvantageous in causing bronchoconstriction and peripheral vasoconstriction. Selective beta-1-antagonist, beta-2-agonist activity would, therefore, appear to be particularly beneficial in offering the advantages of beta-1 blockade plus peripheral vasodilation. The beta-1- and beta-2-receptor actions of drugs are not always clearly identifiable, as in the demonstration of celiprolol's partial beta-2-agonist activity in human beings. This is because, in vivo, cardiovascular reflexes are intact and it has not, so far, been possible to remove endogenous catecholamines. This review summarizes various studies to investigate partial agonist activity, with particular emphasis on celiprolol.