Nicorandil angina

Typical KCO members are diazoxide, pinacidil, cromakalim, and nicorandil. KCOs activate KATP channels by binding to SUR subunits. Diazoxide and nicorandil are clinically used in treatment of PHHI and angina pectoris, respectively. 

From a clinical perspective, some of these PCO classes have attracted initial attention. Diazoxide and minoxidil have been evaluated as antihypertensive agents. These PCOs open K+ channels in the plasma membranes of vascular smooth muscle cells, causing vascular vasodilation, thereby lowering blood pressure. Cromakalim has been investigated as a smooth muscle bronchodilator for the treatment of human asthma. Nicorandil was launched in Japan in 1984 for the treatment of angina because of its perceived ability to promote vasodilation of coronary arteries. Developmental work on these and other PCOs is continuing for indications ranging from hypertension, asthma, urinary incontinence, psychosis, epilepsy, pain, and alopecia (hair loss). 

Nicorandil (7) (see Figure 9.1), the first compound shown to derive some of its pharmacological activity from channel activation [49], has been developed for the treatment of angina. Two additional compounds in this series, KRN2391 (39) (R = NOj) [50], and FK336 (40) [51], appear to be in development for the same indication. The former is more than four orders of magnitude more potent than compound (7) in the vasopressin-treated rat model of angina. 

Nicorandil is an effective vasodilator through two actions. It acts as a nitrate by activating cyclic GMP (see above) but also opens the ATP-dependent potassium channel to allow potassium efflux and h5rperpolarisation of the membrane which reduces calcium ion entry and induces muscular relaxation. It is indicated for use in angina, where it has similar efficacy to p-blockade, nitrates or calcium channel blockade. It is administered orally and is an alternative to nitrates when tolerance to these is a problem, or to the other classes when these are contraindicated by asthma or cardiac failure. Adverse effects to nicorandil are similar to those of nitrates, with headache reported in 35% of patients. It is the only antianginal drug for which at least one trial has demonstrated a beneficial influence upon outcome. ... 

The Impact Of Nicorandil in Angina (IONA) study was a double-blind, randomized, placebo-controlled trial conducted in the United Kingdom in which high-risk patients with stable angina were assigned placebo or nicorandil 10-20 mg. Over a mean follow-up of 1,6 years, significantly more placebo-treated patients suffered an acute coronary syndrome or coronary death (15.5% vs 13.1%,... 

Nicorandil is effective in controUing 69-80% of cases of chronic stable angina when used as monotherapy (6,7). However, clinical experience with nicorandil is still limited, although it has been in general use in Japan for over 8 years. A review of toxicity data has been published (8). 

IONA Study group. Effect of nicorandil on coronary events in patients with stable angina the Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet 2002 359(9314) 1269-75. 

Camm AJ, Maltz MB. A controlled single-dose stndy of the efficacy, dose response and duration of action of nicorandil in angina pectoris. Am J Cardiol 1989 63(21) J61-5. 

Frampton J, Buckley MM, Fitton A. Nicorandil. A review of its pharmacology and therapeutic efficacy in angina pectoris. Drugs 1992 44(4) 625-55. 

In the patient with chronic angina, the drugs commonly used seem to offer important myocardial protection Thus, (3-blockers, ACE inhibitors and most probably angiotensin receptor blockers, statins, Ca2+ channel blockers, all are in their way cardioprotective. Nitrates and more importantly nicorandil are worthwhile options. Trimetazidine and drugs producing a shift towards preferential glucose oxidation would also be a consideration. A number of studies stress that they may produce an improvement in ischemic cardiomyopathy, probably through an anti-inflammatory action.261... 

IONA 151 Nicorandil administration in patients with stable angina 5126 Mortality, coronary events Significant reduction in mortality and frequency of coronary events after a mean of 1.6 years. 

These are a relatively recent development and act by increasing the efflux of potassium ions in smooth muscle cells of blood vessels. This leads to hyperpolarization of vascular smooth muscle thereby reducing the excitability and bringing about vasodilation. The resulting vasodilation in coronary arterioles improves blood flow to the myocardium. This, in combination with a reduction in both afterload (dilation of arteries) and preload (dilation of veins), relieves the angina. Nicorandil is an example of a potassium channel activator. 

Hata N, Takano M, Kunimi T, Kishida H, Takano T. Lack of antagonism between nicorandil and sulfonylurea in stable angina pectoris. IntJ Clin Pharmacol Res (200V) 21, 59-63. 

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