pranidipine and Myocardial-Ischemia

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).

Topics: Animals; Calcium Channel Blockers; Coronary Vessels; Dihydropyridines; Electrocardiography; Hemodynamics; In Vitro Techniques; Male; Models, Biological; Myocardial Contraction; Myocardial Ischemia; Swine; Vasoconstriction