Mechanism of action of clentiazem on human coronary artery and myocardium

Summary

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.