Fendiline: a review of its basic pharmacological and clinical properties.

Abstract

Fendiline is an anti-anginal agent for the treatment of coronary heart disease. Together with other diphenylalkylamines it is sub-classified in the group of lipophilic calcium antagonists. It binds to the calcium channel and to calmodulin with rather similar affinities. Pharmaco-dynamically, it exerts the typical calcium as well as calmodulin antagonistic actions: inhibition of the transmembrane calcium current, smooth muscle relaxation, negative inotropism, cardioprotection, inhibition of calmodulin-activated myosin light-chain kinase and phosphodiesterase. Pharmacokinetics reveal slow onset of action and a long half-life. The anti-anginal and anti-ischaemic efficacy of fendiline has been proven in several placebo-controlled, double-blind trials. It does not interfere with digoxin therapy. Direct comparison with other calcium antagonists by means of controlled studies revealed that its potency is at least equal to that of nifedipine but, in contrast to nifedipine, verapamil, and diltiazem, its anti-anginal action increases during chronic therapy, reaching a steady state of action after 2 to 3 weeks. In addition, the anti-ischaemic and anti-anginal potency is about equal to that of isosorbide dinitrate but fendiline has the advantage of lacking tolerance development. Nevertheless, the data presented indicate that a combination of fendiline with low doses of ISDN may be beneficial. Adverse cardiac and haemodynamic actions, such as increase or decrease in heart rate, disturbance of AV nodal conduction, impairment of cardiac contractile performance or considerable decrease in arterial pressure in hypotensives and normotensives, are lacking.