AI Article Synopsis

  • Atrial fibrillation (AF) is the most common heart rhythm disorder and increases the risk of strokes and heart failure.
  • Current anti-arrhythmic medications have limited effectiveness and can lead to dangerous side effects, such as inducing other heart rhythm issues.
  • The new drug, 14b, specifically targets the GIRK1/4 ion channel to correct AF while reducing side effects, particularly in the central nervous system.

Article Abstract

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and a significant risk factor for ischemic stroke and heart failure. Marketed anti-arrhythmic drugs can restore sinus rhythm, but with limited efficacy and significant toxicities, including potential to induce ventricular arrhythmia. Atrial-selective ion channel drugs are expected to restore and maintain sinus rhythm without risk of ventricular arrhythmia. One such atrial-selective channel target is GIRK1/4 (G-protein regulated inwardly rectifying potassium channel 1/4). Here we describe 14b, a potent GIRK1/4 inhibitor developed to cardiovert AF to sinus rhythm while minimizing central nervous system exposure - an issue with preceding GIRK1/4 clinical candidates.

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http://dx.doi.org/10.1016/j.bmcl.2023.129237DOI Listing

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