Evaluation of KCB-328, a new IKr blocking antiarrhythmic agent in pacing induced canine atrial fibrillation

Europace. 2004 Sep;6(5):384-91. doi: 10.1016/j.eupc.2004.05.006.


Hypothesis: KCB-328 is a new potassium channel blocker, which prolongs action potential duration with exhibition of minimal reverse use dependence. We tested the efficacy and proarrhythmic potential of KCB-328, dofetilide and propafenone in the pacing induced canine model of atrial fibrillation (AF).

Methods: Mongrel dogs in complete heart block were paced for 1-6 weeks to produce AF, and given KCB-328 or dofetilide. A subset then received propafenone 14+/-3 days after testing the first drug.

Results: KCB-328 prolonged right and left atrial (RA and LA) activation times and AF cycle length (CL), terminating AF in 3 of 6 dogs. RA effective refractory period (ERP) and ventricular ERP and QT interval were prolonged. Dofetilide terminated AF in 1/6 dogs, and increased AF CL and ventricular ERP and QT interval. Dofetilide's reverse use dependency on the QT interval was greater than KCB-328. Propafenone prolonged RA and LA activation times and AF CL and terminated AF in 8 of 9 dogs. One death occurred with dofetilide, none with KCB-328 or propafenone.

Conclusion: The spectrum of effect of the three drugs differed significantly: propafenone showed the greatest success in AF termination, and both propafenone and KCB-328 appeared less proarrhythmic than dofetilide in this model.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects
  • Animals
  • Anti-Arrhythmia Agents / administration & dosage*
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / physiopathology
  • Disease Models, Animal
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Heart Atria / drug effects
  • Heart Atria / physiopathology
  • Heart Ventricles / drug effects
  • Heart Ventricles / physiopathology
  • Phenethylamines / administration & dosage*
  • Potassium Channel Blockers / administration & dosage
  • Propafenone / administration & dosage*
  • Random Allocation
  • Sodium Channel Blockers / administration & dosage
  • Sulfonamides / administration & dosage*


  • 1-(2-amino-4-methanesulfonamidophenoxy)-2-(N-(3,4-dimethoxyphenethyl)-N-methylamino)ethane
  • Anti-Arrhythmia Agents
  • Phenethylamines
  • Potassium Channel Blockers
  • Sodium Channel Blockers
  • Sulfonamides
  • Propafenone
  • dofetilide