Effects of Amiodarone and Dronedarone on Voltage-Dependent Sodium Current in Human Cardiomyocytes

Introduction: 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 INa in...

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Published in:Journal of cardiovascular electrophysiology 2003-08, Vol.14 (8), p.885-890
Main Authors: Lalevée, Nathalie, Barrère-lemaire, Stéphanie, Gautier, Patrick, Nargeot, Joël, Richard, Sylvain
Format: Article
Language:English
Subjects:
Adult
Aged
amiodarone
Amiodarone - analogs & derivatives
Amiodarone - pharmacology
Atrial Function - drug effects
Cells, Cultured
Cellular Biology
Dronedarone
human cardiomyocytes
Humans
Ion Channel Gating - drug effects
Ion Channel Gating - physiology
Life Sciences
Membrane Potentials - drug effects
Membrane Potentials - physiology
Middle Aged
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - physiology
Sodium Channels - drug effects
Sodium Channels - physiology
sodium current
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Summary:Introduction: 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 INa in human atrial myocytes. Methods and Results: INa was studied with the whole‐cell, patch clamp technique. Both AM and SR induced a dose‐dependent inhibition of INa recorded at −40 mV from a holding potential of −100 mV. AM inhibited INa by 41%± 11% (n = 4) at 3 μM, and by 80%± 7% (n = 5) at 30 μM. SR produced more potent block, inhibiting INa significantly at only 0.3 μM (23%± 10%, n = 4) and completely (97%± 4%, n = 4) at 3 μM. Both AM and SR had only moderate effects on voltage‐dependent properties of INa (current‐voltage relationship, availability for activation) and had no effect on the current decay kinetics. Conclusion: Both AM and SR inhibit INa 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. (J Cardiovasc Electrophysiol, Vol. 14, pp. 885‐890, August 2003)
ISSN:1045-3873
1540-8167
DOI:10.1046/j.1540-8167.2003.03064.x