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.
Eleclazine是一种新型、具有高度选择性的心脏晚期钠电流抑制剂，IC50值<1μM[1]。Eleclazine通过减少细胞内钠和钙过载，以稳定心膜电位并抑制心律失常，通常用于长QT综合征、心室心动过速等心律失常疾病的治疗和研究[2,3,4]。
在体外，Eleclazine（1μM）预处理离体兔心脏20min，在常温下显著加快了细胞内Ca2+衰减，并抑制了空间不一致交替波（SDA）的诱导[5]。Eleclazine（10μM）处理分离的兔心房肌细胞5min，使异丙肾上腺素（ISO, 15nM）诱导的晚钠电流密度降低了41%（p < 0.05）[6]。
在体内，Eleclazine（0.9mg/kg；静脉输注15min）预处理 Yorkshire 猪，在给药后120min，使肾上腺素（2.0μg/kg，静脉推注1min）诱导的1-2次房性早搏（APBs）发生率降低83%，≥3次APBs发生率降低75%[7]。