Pharmacology and therapeutic effects of nicorandil

Abstract

Nicorandil, a nicotinamide derivative, is an orally efficacious antianginal drug possessing a nitrate moiety in its chemical structure. This drug is an effective and well-tolerated treatment for various types of angina pectoris. Its general efficacy is similar to that of nitrates, with several unique effects on the cardiovascular system. Nicorandil causes sustained dilation of both the arterial resistance and conductive vessels, thus markedly dilating the coronary artery and increasing coronary blood flow. In addition, nicorandil, unlike nitroglycerin or isosorbide dinitrate, possesses little hemodynamic effect on heart rate, blood pressure, or cardiac contractility with clinical doses yielding antianginal effects. The mechanism causing coronary vasodilation has not been completely clarified but appears to be associated partly with increases in c-GMP, as well as the hyperpolarization of the smooth muscle membrane. Nicorandil, in single oral doses of 10-30 mg, has been shown to be effective in chronic stable angina, as assessed objectively by increases in exercise duration and/or the time to onset of ST-segment depression during treadmill exercise. In open studies and controlled efficacy evaluations, nicorandil in daily oral doses of 15-40 mg demonstrated significant effectiveness in the treatment of various types of angina pectoris. Headaches due to vasodilation may occur, and some side effects occurred in 5.1-34% of patients receiving nicorandil, but were generally minor in nature. There was no depressant effect on atrioventricular conduction, which occurs frequently in patients treated with calcium antagonists of the verapamil and diltiazem type. Nicorandil may be effective even in patients with rest and effort angina who do not respond to combination therapy with calcium antagonists and oral nitrates. Thus, nicorandil appears to be a valuable addition to the arsenal of antianginal drugs due to its low incidence of serious side effects.

Effect of Intracoronary Nicorandil Administration on Preventing No-Reflow/Slow Flow Phenomenon During Rotational Atherectomy

“…First, nicorandil also dilates epicardial coronary arteries, and this effect can relieve refractory coronary spasm for which nitrates are not fully effective. 28,29 Second, nicorandil has a longer half-life than adenosine, which has a half-life in human blood of less than 1 s and that may be too short to maintain its effects during RA. Third, adenosine induces coronary steal and negative inotropic effects, which may be detrimental in patients with ischemic heart disease.…”

The Assessment of Nicorandil Effect on the Quality of Life in Patients With Stable Angina in the "Kvazar" Study

“…Приводимые в настоящей статье данные подтвер-ждают наличие у никорандила отчетливого антианги-нального эффекта, доказанного в проводившихся ра-нее исследованиях [13][14][15]. Этот эффект проявился до-стоверным уменьшением количества приступов сте-нокардии и снижением потребности в применении НТГ -основных показателей, отражающих антиангиналь-ное действие лекарственного препарата [16,17].…”

Pharmacological Preconditioning. Focus on Nicorandil

“…Открытие калиевых каналов вызывает гиперполяризацию клеточной мембраны, что ведет к выходу ионов калия из мышечных клеток, приводя к уменьшению поступления в клетки кальция. Такое изменение ионного обмена отмечается, в том числе, в артериях и артериолах, гладкие мышцы которых в результате расслабляются [32], в то время как в КМЦ этот механизм ведет к воспроизведению эффекта ИПРК.…”

“…Возрастает продукция эндоте-лий зависимого фактора релаксации, и, как след-ствие, расслабляются гладкие мышцы кровеносных сосудов. Эти фармакологические эффекты вызывают периферическую вазодилатацию, коронарорасширя-ющее действие и защиту кардиомиоцитов при ише-мии [32,33]. Никорандил практически не влияет на частоту сердечных сокращений, проводящую сис-тему сердца и сократительную способность миокарда.…”