MECHANISM OF ACTION OF CLENTIAZEM ON HUMAN CORONARY-ARTERY AND MYOCARDIUM

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. © 1990 Kluwer Academic Publishers.