title: Beta-blockage therapy and cardiovascular disease. Past, present, and future.
abstract: 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.
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000145:classification / Q000266:history / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy*; D006801:Humans; D014481:United States
chemical_list: D000319:Adrenergic beta-Antagonists