Hans Kuhnis

CGP 28392, a Dihydropyridine Ca2+ Entry Stimulator

Agents termed Ca2+ antagonists or Ca2+ channel blockers (e. g., nifedipine, verapamil, diltiazem) reduce Ca2+ influx through specific channels located in the membranes of vascular smooth muscle and myocardial cells. This action results in vasodilation and decreased myocardial contractility [1-5]. Consequently, this group of agents has clinical value in the therapy of angina pectoris, arrhythmias, and hypertension [6]. Compounds that act to increase Ca2+ influx through specific membrane channels might be expected to possess pharmacological activities opposite to those of the Ca2+ antagonists (e. g., vasoconstriction and increased myocardial contractility) [7]. The first Ca2+ entry stimulator (or Ca2+ agonistic compound) structurally related to nifedipine was YC-170 [8]. Like nifedipine, YC-170 is a 1,4-dihydropyridine derivative, but produced vasopressor effects in anesthetized rats and dogs as well as vasoconstriction in the isolated rabbit aorta. Based on indirect evidence, the authors suggested that these effects were due to an enhanced Ca2+ influx into vascular smooth muscle cells.