Casses of Antianginal Compounds: Old and New—Therapeutic Implications

Abstract

Although the first clear description of angina pectoris was rendered by William Heberden in England in 1803, rational medical therapy for the disorder began to take shape barely 50 years ago. The clinical entity that is now characterized as chronic stable angina is a common condition affecting over 6 million people in the United States alone, with an estimated 400,000 new cases diagnosed every year (1).For many years, nitroglycerin, a potent coronary vasodilator, remained the mainstay of therapy of angina, although the drug could be administered solely by the sublingual route. It provided only temporary relief from angina. Early in the 1950s, it was appreciated that angina may also be controlled by the reduction in myocardial oxygen consumption. As a logical consequence, what followed was the planned synthesis of compounds that exhibited not only coronary vasodilator properties, but also those that had the potential to reduce myocardial oxygen, especially by lowering heart rate.To this end, four important compounds were synthesized in 1962: propranolol and sotalol as 5-blockers, and verapamil and amiodarone as coronary vasodilators (2). These pharmacologically disparate compounds were unexpectedly found to have strikingly distinctive electrophysiologic properties that promptly formed the basis for the classification of antiarrhythmic mechanisms (3-5). Nevertheless, in the first instance, they were all introduced as highly effective antianginal compounds.