Like other calcium-channel blocking agents, diltiazem inhibits the entry of calcium ions in the interior of cardiac and vascular muscle cells. The electromechanical coupling between excitation and contraction is thus interrupted. Diltiazem causes coronary and peripheral vasodilation, slows down the sinus frequency and the atrioventricular nodal conduction, and causes an improvement of the myocardial oxygen supply. Compared to verapamil, the effects of diltiazem are generally slightly less pronounced; therefore the negative activity on the myocardial contractility is also inferior.

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