L- and T-type calcium channel blockade - the efficacy of the calcium channel antagonist mibefradil

Journal of Clinical and Basic Cardiology 1999; 2 (2): 187-201

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Keywords: Kalziumkanalblocker,  L-Typ-Kalziumkanal,  mibefradil,  T-Typ-Kalziumkanal,  calcium channel antagonists,  L-type calcium channel,  mibefradil,  T-type calcium channel

The presence of different subtypes of voltage-dependent calcium channels was recognized about a decade ago. In heart, neurons, vascular smooth muscle and in endocrine cells, so called L-type and T-type currents coexist. These two types of currents are easily discriminated, especially at the single channel level: channel activity in a test pulse is either long-lived (L-type) or transient (T-type). The currently available calcium channel antagonists (CCA) interact predominantly or exclusively with the L-type calcium channel. However, most of the CCA used in the therapy of hypertension and angina pectoris feature to some extent unwanted effects such as negative inotropism, atrioventricular blockade or neurohormonal activation. Mibefradil is a CCA that structurally belongs to a new class of benzimidazolyl tetraline derivatives featuring an inhibition of both L- and T-type calcium channels, with a higher selectivity for T-channels. The compound is a potent antihypertensive and antianginal drug with preferential coronary vasodilative effects, without adverse negative inotropic or positive chronotropic cardiac actions. Thus, mibefradil offers a new concept in calcium channel antagonism, and can be regarded as a pharmacologically important new development within the group of CCA. J Clin Basic Cardiol 1999; 2: 187-201.