Calcium channel drugs: Antagonists and activators

The Ca²⁺ channel antagonists, a chemically heterogeneous group of compounds, have a primary action on potential-dependent Ca²⁺ channels. These agents, which include verapamil, nifedipine, and diltiazem, enjoy prominent clinical use in the treatment of cardiovascular disorders including angina, some arrhythmias, and hypertension. Their relative specificity for Ca²⁺ channnels has made these agents prominent biophysical and biochemical tools. Some 1,4-dihydropyridines, closely related in structure to nifedipine, function as Ca²⁺ channel activators. The several classes of ligands interact at a set of discrete, allosterically linked binding sites that are components of the Ca²⁺ channel protein. The selectivity of action of these compounds may be explained on the basis of the differing affinities of the channel according to state and the existence of several categories of voltage-dependent Ca²⁺ channels with distinct electrophysiologic and pharmacologic characteristics. Future developments will include ligands for other channel classes and the development of neuron-selective agents.