Interaction of the antihypertensive drug felodipine with calmodulin

Despite the marked differences in their chemical structure, members of a heterogeneous group of pharmacological agents are thought specifically to block Ca 2+ influx through calcium channels 1 and thus mediate negative inotropic cardiac effects and vasodilatation. Electrophysiological studies of the myocardium have shown that the slow inward Ca 2+ current is blocked 1 , but the cellular mechanism of these agents in vascular smooth muscle is largely unknown. Felodipine [4-(2,3-dichlorophenyl)-1,4-dihydropyridine-2,6-dimethyl 3,5-dicarboxylic 3-ethylester and 5-methylester)] is a new antihypertensive agent which seems specifically to dilate precapillary resistance vessels in vivo. It is a structural analogue of nifedipine 1 and SKF 24260 2 , both of which have been classified as ‘calcium antagonists’, implying that their vascular as well as myocardial actions are due to a blockade of Ca 2+ influx. However, the findings reported here point rather to an interaction between felodipine and calcium-binding proteins such as calmodulin.