Differences Between Dihydropyridine and Non-Dihydropyridine Calcium Antagonists in Inotropic, Chronotropic, Dromotropic and Vascular Effects: Differences in Underlying Mechanism

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Abstract

It is generally accepted that nifedipine and nicardipine, dihydropyridine (DHP) calcium antagonists (Ca-antagonists), are less cardiodepressant that verapamil and diltiazem, non-dihydropyridine (non-DHP) Ca-antagonists, in therapeutic doses used in the treatment of angina pectoris and/or hypertension. Such a property of nifedipine is indeed one of its advantages over the two non-DHP Ca-antagonists. However, owing to this property nifedipine tends to produce reflex tachycardia which is thought to be one of its undesirable effects [1]. Among new DHP Ca-antagonists developed recently PY 108–068 [2] and PN 200-110 [3] have been claimed less likely to produce reflex tachycardia. Thus, the question arises whether some of DHP Ca-antagonists produced by some modifications of the chemical structure of nifedipine possess a low separation between the vasodilator and the cardiac effects as do verapamil and diltiazem. The present article first treats this question and afterwards discusses mechanisms underlying a high separation between the vasodilator and the cardiac effects in DHP Ca-antagonists. To settle the first question the article treats seven DHP Ca-antagonists, i.e., nifedipine, nicardipine, nimodipine [4, 5], nisoldipine [6], nitrendipine [7, 8], PY 108–068 [2] and PN 200-110 [3] and three non-DHP Ca-antagonists, i.e., verapamil, diltiazem and KB-944 [9, 10].