Similarity and Dissimilarity in the Mode and Mechanism of Action Between Nicorandil and Classical Nitrates

Nicorandil, which is structurally a nitrate and also a nicotinamide, differs from classical nitrates such as nitroglycerin and isosorbide dinitrate in the following respects. It dilates preferentially resistive vessels (arterioles); and it produces the increase in potassium conductance in the membranes of cardiac and some vascular smooth muscle cells that is responsible for its negative inotropic and chronotropic and vasodilator effects. Nicorandil has the following characteristics of a nitrate. (a) It is capable of dilating large conductive coronary arteries, although the effect is weaker than that of classical nitrates. (b) It is capable of reducing venous return, although this effect is less pronounced than that of classical nitrates. (c) It produces an increase in intracellular cyclic guanosine-3',5'-monophosphate (cyclic GMP) in vascular smooth muscle. The activity of nicorandil to increase the membrane potassium conductance resides in the nicotinamide moiety. However, this activity is greatly enhanced by the presence of the nitrate group at an appropriate distance from the nicotinamide group. The nitrate moiety per se has also its own action. The presence of these two pharmacologically active groups in the molecule appears to cause nicorandil to have rather complex cardiovascular actions.