Nicorandil (NRD)

Nicorandil is a vasodilatory drug used to treat angina. Nicorandil stimulates guanylate cyclase to increase formation of cyclic GMP (cGMP). cGMP activates protein kinase G (PKG) which phosphorylates and inhibits GTPase RhoA and decreases Rho-kinase activity. Reduced Rho-kinase activity permits an increase in myosin phosphatase activity, decreasing the calcium sensitivity of the smooth muscle. PKG also activates the sarcolemma calcium pump to remove activating calcium. PKG acts on K+ channels to promote K+ efflux and the ensuing hyperpolarization inhibits voltage-gated calcium channels. Overall, this leads to relaxation of the smooth muscle and coronary vasodilation. K+ATP channel opener: Nicorandil activates K+ATP channel, causing K+ efflux. This hyperpolarizes the cell, which inactivates voltage-gated calcium channels and reduces free intracellular Ca2+.