In-vitro study of the effect of clentiazem on rabbit aorta and on myocardium.
We evaluated the pharmacologic action of clentiazem, a newly synthesized diltiazem derivative, on isolated rabbit aorta and myocardium. In addition to its Ca2+ blocking action, clentiazem demonstrated both vasorelaxing and negative inotropic actions similar to diltiazem. The vasorelaxant action of clentiazem on the tonic phase of KCl-induced contraction (EC50 = 6.13 x 10(-8) M) was 4.5 times more potent than diltiazem (EC50 = 2.77 x 10(-7) M). However, the negative inotropic action of clentiazem (IC50 = 4.34 x 10(-5) M) was similar to diltiazem (IC50 = 3.94 x 10(-5) M). Selectivity ratios, comparing the effectiveness in cardiac muscle with aorta, were clentiazem (708) greater than diltiazem (142). In conclusion, clentiazem is a Ca2+ antagonist and demonstrates greater vasoselectivity than diltiazem. It also has a longer lasting action than diltiazem.
Narita
H
H
Division of Cardiology, Stanford Medical Center, CA.
Ginsburg
R
R
D000818:Animals; D001011:Aorta / Q000187:drug effects*; D003864:Depression, Chemical; D004110:Diltiazem / Q000494:pharmacology / Q000031:analogs & derivatives; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D011817:Rabbits; D013841:Thiazepines / Q000494:pharmacology*; D013997:Time Factors
D013841:Thiazepines; C056595:clentiazem; D011189:Potassium Chloride; D004110:Diltiazem