Nicorandil: animal pharmacology.
Nicorandil, a nicotinamide derivative, is a recently developed, orally active antianginal drug with a cardioprotective activity, and its pharmacologic properties differ from those of conventional antianginal drugs. Nicorandil has the capacity to increase myocardial oxygen supply without increasing oxygen demand by reduction in preload and afterload. In isolated blood-perfused canine heart preparations, when injected into the sinus node, the atrioventricular node or the anterior septal arteries, nicorandil at dose levels doubling blood flow through the respective arteries has virtually no effect on sinus rate, atrioventricular conduction time or contractile force of ventricular muscle. This may indicate that nicorandil possesses a selective effect on the coronary vasculature rather than on the myocardium. Furthermore, the vasospasmolytic activity of nicorandil has been evidenced in in vivo and in vitro experiments. The precise mechanism by which nicorandil develops coronary vasodilating and vasospasmolytic effects remains to be elucidated, but it may be partly inferred by an increase in the potassium conductance in the membrane, a relation with cyclic guanosine monophosphate formation, or inhibition of intracellular calcium ion mobilization in the cell of coronary vascular smooth muscle. Nicorandil possesses a nitrate moiety in its chemical structure. However, it is noted that nicorandil unlike nitrates does not develop tolerance or cross tolerance to other conventional nitrates in terms of blood-pressure lowering effects and coronary vasodilating effects. Thus, nicorandil is likely to have highly beneficial properties in the treatment of angina pectoris.
Sakai
K
K
International Division, Chugai Pharmaceutical Co., Ltd., Tokyo, Japan.
D000787:Angina Pectoris / Q000188:drug therapy; D000818:Animals; D003329:Coronary Vasospasm / Q000188:drug therapy; D004285:Dogs; D004361:Drug Tolerance; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D020108:Nicorandil; D014665:Vasodilator Agents / Q000494:pharmacology* / Q000627:therapeutic use
D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil