Resting, and rate-dependent depression of Vmax of guinea-pig ventricular action potentials by amiodarone and desethylamiodarone

Br J Pharmacol. 1987 Sep;92(1):97-103. doi: 10.1111/j.1476-5381.1987.tb11300.x.


1 The cellular electrophysiological effects of amiodarone and its metabolite desethylamiodarone (DEA) were studied in guinea-pig ventricular myocardium by use of standard microelectrode techniques. 2 Both compounds produced significant increases in action potential duration (Class III antiarrhythmic effect) and decreases in maximum rate of depolarization (Class I effect), at clinically relevant concentrations. 3 The Class I effects were rate-dependent, with small (0-16%) falls in maximum depolarization rate in the absence of stimulation ('resting block') and progressively larger effects at decreasing interstimulus intervals (range 1200-300 ms). 4 The kinetics of onset and offset of the Class I effect in response to a step change in driving rate were quite fast for both drugs (comparable to those reported for Class Ib agents). 5 It is concluded that this unique combination of Class III action plus Class I effects with fast onset and offset kinetics may help explain the great efficacy of amiodarone in antiarrhythmic therapy.

MeSH terms

  • Action Potentials / drug effects
  • Amiodarone / analogs & derivatives*
  • Amiodarone / pharmacokinetics
  • Amiodarone / pharmacology*
  • Animals
  • Female
  • Guinea Pigs
  • Heart / drug effects*
  • In Vitro Techniques
  • Male
  • Myocardium / metabolism


  • desethylamiodarone
  • Amiodarone