Mibefradil: A New Selective T-Channel Calcium Antagonist for Hypertension and Angina Pectoris

Abstract

Calcium antagonists are an established therapy for patients with hypertension and angina pectoris, but their current usage is often limited by their pharmacologic profiles and side effects. Mibefradil is a recently developed calcium antagonist with a unique chemical struc ture, site of action, and set of pharmacologic effects. Unlike currently available calcium antagonists, which block only L-type calcium channels, mibefradil selectively blocks T-type channels as well as L-type channels. It is further distinguished from other calcium antago nists in that it is the first member of a new class of calcium antagonists, the tetralol deriva tives. With chronic oral dosing, mibefradil attains steady-state plasma concentrations within 3-4 days, has a bioavailability of approximately 90%, and a plasma half-life of 17-25 hours. It has a gradual onset of action and can be administered once daily without regard to food intake. It increases coronary blood flow and lowers peripheral vascular resistance. The vasodilatory effects of mibefradil are associated with a lack of inotropic effect on myocardium, lack of neurohormonal activation, and a reduction in heart rate. In clinical trials it has been demonstrated to be an effective agent in the treatment of patients with hyperten sion and angina pectoris, with a good safety and tolerability profile regardless of age, gender, or race.