Beta-blockage therapy and cardiovascular disease. Past, present, and future.

The concept of two patterns of catecholamine activity was first described at the turn of the century by Langely and Dale. In the late 1940s, Ahlquist conceptualized the alpha- and beta-blocking actions of catecholamines. Sir James Black's research in the 1950s led to the introduction of pronethalol and then of propranolol into the therapeutics of angina and arrhythmias. Early beta-receptor blocking compounds were noted not only to be competitive inhibitors of the beta receptor but to have a direct depressant, membrane-stabilizing action. Later compounds, such as pindolol, were noted to have partial agonist activity. Practolol, metoprolol, atenolol, and similar "cardioselective", or beta-selective, drugs were subsequently described. Agents that combine beta blockade with alpha blockade or vasodilator action have been developed recently. There are various therapeutically advantageous pharmacodynamic differences among the beta-blocking drugs, such as less effect of beta 1-selective drugs on bronchial smooth muscle. Lipid solubility, systemic bioavailability, first-pass liver metabolism, renal excretion, and brain penetration are pharmacokinetic properties that further distinguish one agent from another. After the initial predicted therapeutic uses, beta-blocking drugs were used in hypertension and subsequently have been applied in a wide range of cardiovascular conditions. Recent work clearly demonstrating a cardioprotective effect in the post-myocardial infarction period is a major reason that use of the agents is likely to remain high.