Resting, and rate-dependent depression of Vmax of guinea-pig ventricular action potentials by amiodarone and desethylamiodarone.
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.
Pallandi
R T
RT
School of Physiology & Pharmacology, University of New South Wales, Sydney, Australia.
Campbell
T J
TJ
D000200:Action Potentials / Q000187:drug effects; D000638:Amiodarone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism
C036116:desethylamiodarone; D000638:Amiodarone