Myocardial and vascular effects of efonidipine in vitro as compared with nifedipine, verapamil and diltiazem.
1. Effects of efonidipine on isolated myocardial and aortic preparations were compared with those of nifedipine, verapamil and diltiazem. 2. All drugs produced concentration-dependent negative chronotropic effects on isolated guinea-pig atrial preparations. The potency order was efonidipine > or = nifedipine > diltiazem > or = verapamil, EC30 values being 3.08 x 10(-8)M, 3.48 x 10(-8)M, 1.27 x 10(-7)M and 1.47 x 10(-7)M, respectively. 3. Nifedipine, verapamil and diltiazem produced concentration-dependent negative inotropic effects on isolated guinea-pig left atrial preparations. The potency order was nifedipine > verapamil > diltiazem, EC30 values being 4.94 x 10(-8)M, 1.49 x 10(-7)M and 8.03 x 10(-7)M, respectively. Efonidipine, even at 1 microM produced no inotropic effect: 10 microM efonidipine decreased the contractile force by about 20%. 4. All drugs concentration-dependently attenuated the KCl-induced contraction of isolated rat aortic ring preparation. The potency order was nifedipine > efonidipine > verapamil > diltiazem, EC30 values being 2.98 x 10(-9)M, 1.24 x 10(-8)M, 3.96 x 10(-8)M and 2.13 x 10(-7)M, respectively. 5. Thus, efonidipine was demonstrated to be a potent vasodilator with negative chronotropic but minimal negative inotropic activity, which may be of benefit in the treatment of cardiovascular disorders.
Tanaka
H
H
Department of Pharmacology, Toho University School of Pharmaceutical Sciences, Chiba, Japan.
Masumiya
H
H
Sekine
T
T
Sijuku
T
T
Sugahara
M
M
Taniguchi
H
H
Terada
M
M
Saito
W
W
Shigenobu
K
K
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004110:Diltiazem / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D009596:Nitrophenols; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D011189:Potassium Chloride / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C066425:efonidipine; D011189:Potassium Chloride; D014700:Verapamil; D004110:Diltiazem; D009543:Nifedipine