Calcium antagonists: definition and mode of action

Abstract

The term “calcium antagonist” has been used for more than a decade to describe a group of drugs whose negative inotropism is overcome by calcium. Because this term lacks specificity with respect to a precise mode of action, and implies a classical receptor-agonist-antagonist relationship, its continued use should be questioned. Drugs belonging to this group are verapamil, D600, nifedipine and diltiazem. They inhibit the slow inward current of the action potential and would more appropriately be called “slow channel inhibitors”. The group is heterogenous and may have to be subclassified. The negative inotropism of these drugs can be attributed to a reduction of the slow calcium current. The function of most intracellular organelles is unaffected. Studies with radioactively labelled verapamil show tight binding to glycolipids or glycoproteins in the sarcolemma. Consequent change in the conformational state of the cell membrane could inhibit the slow calcium current. The ability of these drugs to protect heart muscle against the deleterious effects of ischaemia and reperfusion may reflect their negative inotropism, with consequent maintenance of tissue ATP above the levels needed to maintain intracellular Ca²⁺ homeostasis, rather than a direct inhibitory effect on calcium influx during ischaemia or on reperfusion.