Cardiac Na⁺/Ca²⁺ exchange stimulators among cardioprotective drugs

We previously reviewed our study of the pharmacological properties of cardiac Na⁺/Ca²⁺ exchange (NCX1) inhibitors among cardioprotective drugs, such as amiodarone, bepridil, dronedarone, cibenzoline, azimilide, aprindine, and benzyl-oxyphenyl derivatives (Watanabe et al. in J Pharmacol Sci 102:7-16, 2006). Since then we have continued our studies further and found that some cardioprotective drugs are NCX1 stimulators. Cardiac Na⁺/Ca²⁺ exchange current (I_NCX1) was stimulated by nicorandil (a hybrid ATP-sensitive K⁺ channel opener), pinacidil (a non-selective ATP-sensitive K⁺ channel opener), flecainide (an antiarrhythmic drug), and sodium nitroprusside (SNP) (an NO donor). Sildenafil (a phosphodiesterase-5 inhibitor) further increased the pinacidil-induced augmentation of I_NCX1. In paper, here I review the NCX stimulants that enhance NCX function among the cardioprotective agents we examined such as nicorandil, pinacidil, SNP, sildenafil and flecainide, in addition to atrial natriuretic (ANP) and dofetilide, which were reported by other investigators.