The Pharmacology of Calcium Antagonists

Abstract

Calcium antagonists are a group of drugs with widely varying pharmacological properties and a broad range of therapeutic applications. At least four major types of calcium antagonists can be distinguished on the basis of chemical structures and profile of activity: phenylalkylamines, dihydropyridines, benzothiazepines, and piperazines. Each of these subgroups interferes with calcium transport over excitable membranes. Different types of calcium channels have been identified. The molecular properties as well as the differential binding characteristics of the subgroups of calcium antagonists have been defined. Although all calcium antagonists share an ability to dilate blood vessels, there is a marked difference in potency and selectivity, even within the individual subgroups. The dihydropyridines are relatively selective antagonists of vascular smooth muscle cell calcium uptake. They have a marked sensitivity to inhibit myogenic vascular tone. This may contribute to their predominant in vivo effect on vascular beds characterized by a relatively high myogenic tone, such as the coronary and skeletal muscle beds. Additional mechanisms contributing to the antihypertensive mode of action of dihydropyridines may include an interference with neural control of the circulation as well as intrarenal actions to promote electrolyte and water excretion. A relatively unexplored area of potential importance in the long-term mode of antihypertensive action of calcium antagonists is their effect on the structural design of blood vessels.