The sodium-hydrogen exchanger isoform-1 (NHE-1) is the most predominant isoform of the Na+/H+ exchanger and is expressed in the heart where it contributes to cardiomyocyte pH homeostasis. It plays an important role in the myocardial response to ischemia-reperfusion. Zoniporide inhibits human NHE-1 with an IC50 value of 14 nM, displaying greater than 150-fold selectivity over other NHE isoforms. It has been shown to reduce infarct size in a rabbit myocardial ischemia-reperfusion model without adversely affecting hemodynamics or cardiac function. In isolated heart, zoniporide reduced infarct size with an EC50 value of 0.25 nM.
