Second-generation calcium antagonists: search for greater selectivity and versatility

Abstract

Calcium antagonists have a variable specificity for cardiac and peripheral activity. Based on such activity, these compounds, new and old, can be classified into 4 categories. Type 1 agents, typified by verapamil, its congeners (tiapamil and gallopamil) and diltiazem, prolong atrioventricular nodal conduction and refractoriness with little effect on ventricular or atrial refractoriness. These actions, to a large extent, account for the antiarrhythmic properties of this type of calcium antagonists. Type 2 agents include nifedipine and other dihydropyridines. In vivo, these agents are devoid of electrophysiologic effects in usual doses and concentrations. They are potent peripheral vasodilators with some selectivity of action for different vascular beds; their overall hemodynamic effects are dominated by this peripheral vasodilatation and reflex augmentation of sympathetic reflexes. Type 3 agents are flunarizine and cinnarizine (piperazine derivatives); in vitro and vivo, they are potent dilators of peripheral vessels, with no corresponding calcium-blocking actions in the heart. Type 4 agents (perhexiline, lidoflazine and bepridil) have a broader pharmacologic profile; they block calcium fluxes in the heart, in the peripheral vessels or in both. They may inhibit the fast channel in the heart and have other electrophysiologic actions. A clear understanding of the varied pharmacologic properties of the different classes of calcium antagonists is likely to provide a rational basis for the use of the newer agents in clinical therapeutics.(ABSTRACT TRUNCATED AT 250 WORDS)