[Effects of pranidipine (OPC-13340), a novel 1,4-dihydropyridine derivative Ca-antagonist, on isolated porcine coronary contraction and acute myocardial ischemia in the pig].
Pranidipine (OPC-13340) is a novel, potent and long-acting 1,4-dihydropyridine derivative Ca-antagonist being developed for clinical use as an antihypertensive and antianginal drug. Pranidipine at concentrations of 10(-9) - 10(-6) M suppressed the contraction induced by serotonin (10(-8) - 10(-5) M) or histamine (10(-8) - 10(-4) M) in isolated porcine coronary arteries in a non-competitive and concentration-dependent manner. The potency of this effect of pranidipine was almost similar to that of nifedipine. In anesthetized open-chest pigs with coronary artery occlusion, pranidipine at a dose of 10 micrograms/kg, i.v. lowered blood pressure and increased heart rate, peak dP/dt and % segment shortening of the non-ischemic zone before occlusion. Pranidipine inhibited the ST elevation of the electrocardiogram and the increase in left ventricular end-diastolic pressure during ischemia. These results suggest that pranidipine might relieve symptoms via inhibition of coronary spasm and reduce myocardial ischemia due to reduction of both preload (left ventricular end-diastolic pressure) and afterload (blood pressure).
Ohura
M
M
2nd Tokushima Institute of New Drug Research, Otsuka Pharmaceutical Co., Japan.
Mori
T
T
Watanabe
K
K
Ikezono
K
K
Nakayama
N
N
Tominaga
M
M
Yabuuchi
Y
Y
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D003331:Coronary Vessels / Q000187:drug effects*; D004095:Dihydropyridines / Q000494:pharmacology*; D004562:Electrocardiography; D006439:Hemodynamics / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008954:Models, Biological; D009200:Myocardial Contraction / Q000187:drug effects; D017202:Myocardial Ischemia / Q000188:drug therapy*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C048161:pranidipine