<unk>  is an anti-angina medication that has the dual properties of a nitrate and ATP-sensitive channel agonist. In humans, the nitrate action of<unk>  dilates the large coronary arteries at low plasma concentrations. At high plasma concentrations<unk>  reduces coronary vascular resistance, which is associated with increased ATP-sensitive channel (KATP) opening.<unk>  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 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. The effect of<unk>  as a vasodilator is mainly attributed to its nitrate property. Yet,<unk>  is effective in cases where nitrates, such as nitroglycerine, are not effective. Studies show that this is due to its KATP channel agonist action which causes pharmacological preconditioning and provides cardioprotective effects against ischemia.<unk>  activates KATP channels in the mitochondria of the myocardium, which appears to relay the cardioprotective effects, although the mechanism is still unclear. In experimental animal models of the Long QT syndrome,<unk>  normalizes the prolonged cardiac action potential duration and the QT interval.
Nicorandil
Avacopan
Mitapivat
Acebutolol
Stiripentol
Lumasiran
Eluxadoline
Tetryzoline