Nicorandil: A Potassium Channel Opening Drug for Treatment of Ischemic Heart Disease

Abstract

Nicorandil is the first oral potassium channel activating drug to be used for the treatment of symptomatic coronary artery disease. It appears to relax vascular smooth muscle through membrane hyperpolarization via increased transmembrane potassium conductance and, like nitrates, through an increase in intracellular cyclic GMP. In addition, nicorandil, in a nitrate-like manner, dilates normal and stenotic coronary arteries and reduces both ventricular preload and afterload. In contrast to nitrates, however, nicorandil does not appear to cause tolerance with long-term administration. In placebo and comparison clinical trials, nicorandil has demonstrated some efficacy and safety in patients with both stable and vasospastic angina pectoris, and it was found to be a myocardial protective agent in animal studies. The antianginal activity of nicorandil, however, is relatively short lived after dosing, which will necessitate the development of extended-release formulations of the drug.

Dual mechanism of action of nicorandil on rabbit corpus cavernosal smooth muscle tone

“…The ®ndings of the mode and mechanism of action of nicorandil suggest that compounds like nicorandil with a dual mechanism may be of clinical importance for male erectile dysfunction because ef®cacy is expected to be increased by employing two independent mechanisms, when drug is administered locally to achieve high enough doses that both K ATP channel opening and guanylate cyclase activation are involved. Nicorandil is a potent vasodilating agent for the treatment of myocardial hypoxia and two postulated mechanisms of action on different parts of the vascular systems have also been reported, 12,25 the nitrate-like effect of nicorandil inducing the vasodilation of large coronary arteries, and its opening action on K ATP channels dilating the coronary resistance vessels.…”

“…11 Nicorandil (N-(2-hydroxyethyl)nicotinamide nitrate ester) is an orally ef®cacious anti-anginal drug. 12 While this agent has been shown to relax human corpus cavernosum, 13 the mechanism under-lying this effect remains to be fully elucidated. The present study was designed to investigate the mechanism of action of nicorandil in rabbit corpus cavernosum.…”

Potassium channel activation and relaxation by nicorandil in rat small mesenteric arteries

“…The vasodilator nicorandil is a nicotinamide derivative used clinically for the treatment of angina (Frampton et al, 1992;Goldschmidt et al, 1996). Nicorandil has been proposed to have at least two mechanisms of action: opening K + channels and also having a nitrovasodilator action, activating guanylyl cyclase (GC) and so increasing guanosine 3' : 5'-cyclic monophosphate (cyclic GMP) (Holzmann et al, 1992;Frampton et al, 1992).…”

Usefulness of Massive Oral Nicorandil in a Patient with Variant Angina Refractory to Conventional Treatment.

“…Nicorandil is a nicotinamide ester with a dual mechanism of action (13)(14)(15)(16)(17). Its distinctive pharmacological effect is to open ATP-sensitive potassium channels, thereby dilating peripheral and coronary resistance arterioles; but it also possesses a nitrate moiety which dilates systemic veins and epicardial coronary arteries.…”