Membrane activity of class III antiarrhythmic compounds; a comparison between ibutilide, d-sotalol, E-4031, sematilide and dofetilide

Eur J Pharmacol. 1993 Mar 30;234(1):43-53. doi: 10.1016/0014-2999(93)90704-l.

Abstract

This study compares the membrane activity of ibutilide, d-sotalol, sematilide, E-4031 and dofetilide on single ventricular cells under identical experimental conditions. We found that ibutilide and dofetilide produced a 'bell-shaped' concentration-dependent effect on action potential duration. Ionic current measurement showed that ibutilide, at 10(-8) M, increased a late inward current; the other compounds had either no effect or decreased it. Moreover, only ibutilide, at a high concentration of 10(-5) M, increased an outward current, as oppose to a uniform depression of IK by d-sotalol, sematilide, E-4031 and dofetilide, and the depression of IK by the latter compounds could be reversed by 10(-5) M ibutilide. Finally, low concentration of ibutilide could further prolong the action potential duration that had already been prolonged by a K+ channel blocker, but a high concentration of ibutilide did just the opposite by reversing the prolongation caused by K+ channel blockers. Therefore, action potentials agree well with the ionic current results. Possible mechanistic advantage of ibutilide over K+ channel blockers was discussed.

Publication types

  • Comparative Study

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Anti-Arrhythmia Agents / pharmacology*
  • Guinea Pigs
  • Heart / drug effects*
  • In Vitro Techniques
  • Membrane Potentials / drug effects
  • Phenethylamines / pharmacology
  • Piperidines / pharmacology
  • Potassium Channels / drug effects
  • Procainamide / analogs & derivatives
  • Procainamide / pharmacology
  • Pyridines / pharmacology
  • Sotalol / pharmacology
  • Sulfonamides / pharmacology

Substances

  • Anti-Arrhythmia Agents
  • Phenethylamines
  • Piperidines
  • Potassium Channels
  • Pyridines
  • Sulfonamides
  • sematilide
  • E 4031
  • ibutilide
  • Sotalol
  • Procainamide
  • dofetilide