Introduction It has been known since the late 1800s that calcium influx was necessary for the contraction of smooth and cardiac muscle.The discovery of a calcium channel in cardiac muscle was followed by the finding of several different types of calcium channels in different tissues.The discovery of these channels made possible the development of clinically useful blocking drugs.Although the successful therapeutic blockers developed to date have been exclusively L-type channel blockers,selective blockers of other types of calcium channels are under intensive investigation. Chemistry Pharmacokinetics Verapamil,the first clinically useful member of this group,was the result of attempts to synthesize more active analogs of papaverine,a vasodilator alkaloid found in the opium poppy.Since then,dozens of agents of varying structure have been found to have the same fundamental pharmacologic action.Three chemically dissimilar calcium channel blockers are shown in Figure 4.Nifedipine is the prototype of the dihydropyridine family of calcium channel blockers;dozens of molecules in this family have been investigated,and seven are currently approved in the USA for angina and other indications.Nifedipine is the most extensively studied of this group, but the properties of the other dihydropyridines can be assumed to be similar to it unless otherwise noted. The calcium channel blockers are orally active agents and are characterized by high first-pass effect,high plasma protein binding,and extensive metabolism.Verapamil and diltiazem are also used by the intravenous route.13 Introduction It has been known since the late 1800s that calcium influx was necessary for the contraction of smooth and cardiac muscle. The discovery of a calcium channel in cardiac muscle was followed by the finding of several different types of calcium channels in different tissues. The discovery of these channels made possible the development of clinically useful blocking drugs. Although the successful therapeutic blockers developed to date have been exclusively L-type channel blockers, selective blockers of other types of calcium channels are under intensive investigation. Chemistry  Pharmacokinetics Verapamil, the first clinically useful member of this group, was the result of attempts to synthesize more active analogs of papaverine, a vasodilator alkaloid found in the opium poppy. Since then, dozens of agents of varying structure have been found to have the same fundamental pharmacologic action. Three chemically dissimilar calcium channel blockers are shown in Figure 4. Nifedipine is the prototype of the dihydropyridine family of calcium channel blockers; dozens of molecules in this family have been investigated, and seven are currently approved in the USA for angina and other indications. Nifedipine is the most extensively studied of this group, but the properties of the other dihydropyridines can be assumed to be similar to it unless otherwise noted. The calcium channel blockers are orally active agents and are characterized by high first-pass effect, high plasma protein binding, and extensive metabolism. Verapamil and diltiazem are also used by the intravenous route