DOFETILIDE-D4

Description

Dofetilide-d₄ is intended for use as an internal standard for the quantification of dofetilide by GC- or LC-MS. Dofetilide is a class III antiarrhythmic agent that prolongs cardiac action potential duration by selectively inhibiting the rapidly activating inward rectifying component of net delayed rectifier K⁺ current (IC₅₀ = 31.5 nM in guinea pig cardiomyocytes). However, at 1 μM, dofetilide has pro-arrhythmic activity, inducing early afterdepolarizations (prolonged repolarization) in cell models and Torsade de Pointes in a rabbit screen for proarrhythmic properties when administered at a dose of 10 mg/kg. Formulations containing dofetilide have been used in the treatment of highly symptomatic atrial fibrillation and the conversion of flutter to normal sinus rhythm.

Chemical Properties

White Crystalline Solid

Uses

Potassium channel blocker.

Uses

Dofetilide-d4 is intended for use as an internal standard for the quantification of Dofitilide by GC- or LC-mass spectrometry.

References

[1] N K JURKIEWICZ  M C S. Rate-dependent prolongation of cardiac action potentials by a methanesulfonanilide class III antiarrhythmic agent. Specific block of rapidly activating delayed rectifier K+ current by dofetilide.[J]. Circulation research, 1993, 72 1: 75-83. DOI: 10.1161/01.res.72.1.75
[2] L NALOS. Comparison of the IKr blockers moxifloxacin, dofetilide and E-4031 in five screening models of pro-arrhythmia reveals lack of specificity of isolated cardiomyocytes[J]. British Journal of Pharmacology, 2011, 165 2: 467-478. DOI: 10.1111/j.1476-5381.2011.01558.x
[3] ALBERT DUNNINK. Ventricular remodelling is a prerequisite for the induction of dofetilide-induced torsade de pointes arrhythmias in the anaesthetized, complete atrio-ventricular-block dog.[J]. Europace, 2012, 14 3: 431-436. DOI: 10.1093/europace/eur311