Mechanism of action of clentiazem on human coronary artery and myocardium

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Abstract
We evaluated the pharmacologic action of clentiazem, a new diltiazem derivative, on isolated human coronary artery and right ventricular trabeculae. In addition to its Ca2+ blocking action, clentiazem demonstrated both vasorelaxing and negative inotropic actions, similar to our reference Ca2+ antagonists. The coronary vasorelaxing action of clentiazem on the tonic KCl contraction (EC50=2.21×10−7M) was 3.1 times more potent than diltiazem (EC50=6.94×10−7M) and 28.8 times less potent than nifedipine (EC50=7.67×10−9 M). The negative inotropic action of clentiazem (IC50=8.78×10−6 M) was similar to diltiazem (IC50=7.18×10−6M) and was 21.1 times less potent than nifedipine (IC50=3.98×10−7 M). Selectivity ratios, comparing the effectiveness in cardiac muscle to coronary artery, were nifedipine (51.9)>clentiazem (39.7)>diltiazem (10.3), when calculated from the EC50 and the IC50, and clentiazem (24.2)>nifedipine (15.9)>diltiazem (9.3), when calculated from the EC20 and the IC20. In conclusion, clentiazem is a Ca2+ antagonist and demonstrates comparable vasoselectivity to the 1,4-dihydropyridine derivative, nifedipine. Moreover, it has longer lasting áction than diltiazem.