Effect of SEA0400, a novel inhibitor of sodium‐calcium exchanger, on myocardial ionic currents

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Abstract
The effects of 2‐[4‐[(2,5‐difluorophenyl) methoxy]phenoxy]‐5‐ethoxyaniline (SEA0400), a newly synthesized Na+‐Ca2+ exchanger (NCX) inhibitor, on the NCX current and other membrane currents were examined in isolated guinea‐pig ventricular myocytes and compared with those of 2‐[2‐[4‐(4‐nitrobenzyloxy) phenyl]ethyl]isothiourea (KB‐R7943). SEA0400 concentration‐dependently inhibited the NCX current with a 10 fold higher potency than that of KB‐R7943; 1 μM SEA0400 and 10 μM KB‐R7943 inhibited the NCX current by more than 80%. KB‐R7943, at 10 μM, inhibited the sodium current, L‐type calcium current, delayed rectifier potassium current and inwardly rectifying potassium current by more than 50%, but SEA0400 (1 μM) had no significant effect on these currents. These results indicate that SEA0400 is a potent and highly selective inhibitor of NCX, and would be a powerful tool for further studies on the role of NCX in the heart and the therapeutic potential of its inhibition. British Journal of Pharmacology (2002) 135, 1096–1100; doi:10.1038/sj.bjp.0704574