Effects of amiodarone and dronedarone on voltage-dependent sodium current in human cardiomyocytes.
Effect of Dronedarone on Cardiac Na Current.


BACKGROUND
Amiodarone (AM) is a highly effective antiarrhythmic agent used in the management of both atrial and ventricular arrhythmias. Its noniodinated analogue dronedarone (SR) may have fewer side effects than AM. In this study, we compared the effects of AM and SR on the sodium current I(Na) in human atrial myocytes.


RESULTS
INa was studied with the whole-cell, patch clamp technique. Both AM and SR induced a dose-dependent inhibition of I(Na) recorded at -40 mV from a holding potential of -100 mV. AM inhibited I(Na) by 41%+/- 11% (n = 4) at 3 microM, and by 80%+/- 7% (n = 5) at 30 microM. SR produced more potent block, inhibiting INa significantly at only 0.3 microM (23%+/- 10%, n = 4) and completely (97%+/- 4%, n = 4) at 3 microM. Both AM and SR had only moderate effects on voltage-dependent properties of I(Na) (current-voltage relationship, availability for activation) and had no effect on the current decay kinetics.


CONCLUSIONS
Both AM and SR inhibit I(Na) significantly in single human atrial cells, showing that the two drugs have Class I antiarrhythmic properties. The acute effects of SR are more potent than those of AM. The study supports the idea that the iodinated form of the molecule has no part in the acute effect of AM on Na+ channels.
Lalevée
Nathalie
N
CNRS UPR 1142, Institut de Génétique Humaine, Montpellier, France.
Nargeot
Joël
J
Barrére-Lemaire
Stéphanie
S
Gautier
Patrick
P
Richard
Sylvain
S
D000328:Adult; D000368:Aged; D000638:Amiodarone / Q000031:analogs & derivatives* / Q000494:pharmacology*; D016275:Atrial Function / Q000187:drug effects; D002478:Cells, Cultured; D000077764:Dronedarone; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008875:Middle Aged; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000502:physiology*; D015222:Sodium Channels / Q000187:drug effects* / Q000502:physiology*
D015222:Sodium Channels; D000077764:Dronedarone; D000638:Amiodarone