Nicorandil (SG-75)(Ikorel) acts by relaxing the smooth muscle of the blood vessels, especially those of the venous system. It undertakes this through two methods. Firstly, by activating potassium channels, and secondly by donating nitric oxide to activate the enzyme guanylate cyclase. Guanylate cyclase causes activation of cGMP leading to both arterial and venous vasodilatation by de-phosphorylation of the myosin light chain.

Nicorandil (100 mM) increases Flavoprotein oxidation but not membrane current; a 10-fold higher concentration recruits both mitoK(ATP) and surfaceK(ATP) channels. Nicorandil bluntes the rate of cell death in a pelleting model of ischemia; this cardioprotective effect is prevented by the mitoK(ATP) channel blocker 5-hydroxydecanoate but is unaffected by the surfaceK(ATP) channel blocker HMR1098. [1] Nicorandil (100 mM) suppresses TUNEL positivity, cytochrome c translocation, caspase-3 activation and dissipation of mitochondrialinner membrane potential (Delta(Psi)(m)). Nicorandil prevents Delta(Psi)(m) depolarization in a concentration-dependent manner (EC(50) approximately 40 mM, with saturation by 100 mM), as shown by fluorescence-activated cell sorter analysis of cells stained with a fluorescent Delta(Psi)(m)-indicator, tetramethylrhodamine ethyl ester (TMRE). [2] Nicorandil activates a weakly inwardly-rectifying, glibenclamide-sensitive 80 pS K+ channel in both the transfected cells. Nicorandil preferentially activates the K(ATP) channels containing SUR2B in HEK293T cells. [3] Nicorandil (100 mM) significantly suppresses the number of cells with TUNEL-positive nuclei and the increase in caspase-3 activity induced by 20 mM Water2. Nicorandil prevents the loss of DeltaPsim induced by Water2 in a concentration-dependent manner. [4]