ArticlePloS one2023
Mechanisms underlying the antiarrhythmic effect of ARumenamide-787 in experimental models of the J wave syndromes and hypothermia.
Article in PloS one, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 5 papers.
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5 citing papers in PubMed, 4 citations in OpenAlex.
- ARumenamides as Multitarget Ion Channel Modulators: Insights from Fenestration-Focused Docking, ADMET Profiling, and Molecular Dynamics.International journal of molecular sciences · 2026Article
- Cardiac Channelopathies: Clinical Diagnosis and Promising Therapeutics.Journal of the American Heart Association · 2025Review
- Voltage-gated sodium channels in excitable cells as drug targets.Nature reviews. Drug discovery · 2025Review
- Primary Electrical Heart Disease-Principles of Pathophysiology and Genetics.International journal of molecular sciences · 2024Review
- Article
Corrections and comments
- Erratum issued
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundBrugada (BrS) and early repolarization syndromes (ERS), the so-called J wave syndromes (JWS), are associated with life-threatening ventricular arrhythmias. Pharmacologic approaches to therapy are currently limited. In this study, we examine the effects of ARumenamide-787 (AR-787) to suppress the electrocardiographic and arrhythmic manifestations of JWS and hypothermia.
methodsWe studied the effects of AR-787 on INa and IKr in HEK-293 cells stably expressing the α- and β1-subunits of the cardiac (NaV1.5) sodium channel and hERG channel, respectively. In addition, we studied its effect on Ito, INa and ICa in dissociated canine ventricular myocytes along with action potentials and ECG from coronary-perfused right (RV) and left (LV) ventricular wedge preparations. The Ito agonist, NS5806 (5-10 μM), ICa blocker, verapamil (2.5 μM), and INa blocker, ajmaline (2.5 μM), were used to mimic the genetic defects associated with JWS and to induce the electrocardiographic and arrhythmic manifestations of JWS (prominent J waves/ST segment elevation, phase 2 reentry and polymorphic VT/VF) in canine ventricular wedge preparations.
resultsAR-787 (1, 10 and 50 μM) exerted pleiotropic effects on cardiac ion channels. The predominant effect was inhibition of the transient outward current (Ito) and enhancement of the sodium channel current (INa), with lesser effects to inhibit IKr and augment calcium channel current (ICa). AR-787 diminished the electrocardiographic J wave and prevented and/or suppressed all arrhythmic activity in canine RV and LV experimental models of BrS, ERS and hypothermia.
conclusionsOur findings point to AR-787 as promising candidate for the pharmacologic treatment of JWS and hypothermia.
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