Eleclazine is a novel, highly selective inhibitor of the cardiac late sodium current, with an IC50 value of <1μM[1]. By reducing intracellular sodium and calcium overload, Eleclazine stabilizes the cardiac membrane potential and suppresses arrhythmias, and is commonly used in the treatment and research of arrhythmic conditions such as long QT syndrome and ventricular tachycardia[2,3,4].
In vitro, Eleclazine (1μM) pretreatment of isolated rabbit hearts for 20min significantly accelerated intracellular Ca2+ decay and suppressed the induction of spatially discordant alternans (SDA) under normothermic conditions[5]. Eleclazine (10μM) treatment of isolated rabbit atrial myocytes for 5min reduced the late sodium current density induced by isoproterenol (ISO, 15nM) by 41% (p < 0.05)[6].
In vivo, Yorkshire pigs pretreated with Eleclazine (0.9mg/kg; intravenous infusion over 15min) showed an 83% reduction in the incidence of 1-2 beat atrial premature beats (APBs) and a 75% reduction in ≥3 APBs induced by epinephrine (2.0μg/kg, intravenous bolus over 1min) at 120min after Eleclazine administration[7].
References:
[1] BACIC D, CARNEIRO J S, BENTO A A, et al. Eleclazine, an inhibitor of the cardiac late sodium current, is superior to flecainide in suppressing catecholamine-induced ventricular tachycardia and T-wave alternans in an intact porcine model[J]. Heart Rhythm, 2017, 14(3): 448-454.
[2] RAJAMANI S, LIU G, EL-BIZRI N, et al. The novel late Na+ current inhibitor, GS-6615 (eleclazine) and its anti-arrhythmic effects in rabbit isolated heart preparations[J]. British Journal of Pharmacology, 2016, 173(21): 3088-3098.
[3] POTET F, EGECIOGLU D E, BURRIDGE P W, et al. GS-967 and eleclazine block sodium channels in human induced pluripotent stem cell-derived cardiomyocytes[J]. Molecular Pharmacology, 2020, 98(5): 540-547.
[4] ZHANG Y, WANG H M, WANG Y Z, et al. Increment of late sodium currents in the left atrial myocytes and its potential contribution to increased susceptibility of atrial fibrillation in castrated male mice[J]. Heart Rhythm, 2017, 14(7): 1073-1080.
[5] LEE H L, CHANG P C, WO H T, et al. Eleclazine suppresses ventricular fibrillation in failing rabbit hearts with ischemia-reperfusion injury undergoing therapeutic hypothermia[J]. Pharmacology, 2025, 110(3): 151-164.
[6] LIU X, REN L, YU S, et al. Late sodium current in synergism with Ca2+/calmodulin-dependent protein kinase II contributes to β-adrenergic activation-induced atrial fibrillation[J]. Philosophical Transactions of the Royal Society B: Biological Sciences, 2023, 378(1879).
[7] FULLER H, JUSTO F, NEARING B D, et al. Eleclazine, a new selective cardiac late sodium current inhibitor, confers concurrent protection against autonomically induced atrial premature beats, repolarization alternans and heterogeneity, and atrial fibrillation in an intact porcine model[J]. Heart Rhythm, 2016, 13(8): 1679-1686.