Class III antiarrhythmic agents have a lot of potential but a long way to go. Reduced effectiveness and dangers of reverse use dependence

Circulation. 1990 Feb;81(2):686-90. doi: 10.1161/01.cir.81.2.686.


With regard to currently available class III agents, although their class III effect may reduce the likelihood of tachycardia initiation, their reverse use-dependent prolongation of action potential duration reduces their effectiveness during tachycardias and may even render them proarrhythmic, especially after long diastolic intervals. In contrast, agents that exhibit normal use-dependent prolongation of refractoriness hold great promise: While having relatively less effects on the normal heart beat, they could induce self-termination of a tachycardia. Prolongation of refractoriness can be achieved by lengthening of action potential duration and delaying recovery of excitability. Combination of these drug actions may yield important clinical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials / drug effects
  • Anti-Arrhythmia Agents* / therapeutic use
  • Anti-Arrhythmia Agents* / toxicity
  • Arrhythmias, Cardiac / chemically induced
  • Heart Conduction System / drug effects*
  • Humans
  • Models, Cardiovascular
  • Potassium Channels / drug effects
  • Sodium Channels / drug effects
  • Tachycardia / drug therapy*


  • Anti-Arrhythmia Agents
  • Potassium Channels
  • Sodium Channels