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 x 10(-7) M) was 3.1 times more potent than diltiazem (EC50 = 6.94 x 10(-7) M) and 28.8 times less potent than nifedipine (EC50 = 7.67 x 10(-9) M). The negative inotropic action of clentiazem (IC50 = 8.78 x 10(-6) M) was similar to diltiazem (IC50 = 7.18 x 10(-6) M) and was 21.1 times less potent than nifedipine (IC50 = 3.98 x 10(-7) M). Selectivity ratios, comparing the effectiveness in cardiac muscle to coronary artery, were nifedipine (51.9) greater than clentiazem (39.7) greater than diltiazem (10.3), when calculated from the EC50 and the IC50, and clentiazem (24.2) greater than nifedipine (15.9) greater than 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 action than diltiazem.
Narita
H
H
Division of Cardiology, Stanford Medical Center, CA.
Zera
P H
PH
Ginsburg
R
R
D000293:Adolescent; D000328:Adult; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002648:Child; D003331:Coronary Vessels / Q000187:drug effects*; D003864:Depression, Chemical; D004110:Diltiazem / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects*; D013841:Thiazepines / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D013841:Thiazepines; C056595:clentiazem; D004110:Diltiazem