Nicorandil, coronary vasodilation

Nicorandil. Nicorandil is a potassium channel opener that can lower blood pressure 21, 20, and 29 mm Hg after single oral doses of 10, 20, and 30 mg, respectively (250). There are no significant changes ia heart rate. Headache is the primary side effect. Nicorandil has potent coronary vasodilator effects. It causes sustained vasodilation of arteriolar resistance and venous capacitance blood vessels, thus reduciag cardiac preload and aftedoad. 

The coronary vasodilator response of nicorandil is potentiated by dipjridamole (34). 

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 is a potent vasodilator with anti-spasmodic properties. Its cardiovascular effects are mainly characterised by dilatation of large coronary arteries in combination with reduction of preload and afterload. It has a dual mode of action, activating ATP-dependent K+ channels and a nitrate-like effect. 

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. 

Nicotinic acid and its reduced form, nicotinyl alcohol, have been used for years in attempts to manage peripheral vascular disease. However, nicotinic acid and the alcohol (which is metabolized to the acid) have weak vasodilating activity. At tolerated doses they probably exhibit some activity on dermal blood vessels. The nitrate ester of N-(p-hydrox-yethyl)nicotinamide, nicorandil, was developed in Japan as an antianginal agent. The drug has coronary and peripheral vasodilating properties as well as spasmolytic effects. It thus acts as a classical nitrate. Whether the molecular mechanisms are the same has not been established. 

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