Electrophysiological effects of dronedarone (SR 33589), a noniodinated amiodarone derivative in the canine heart: comparison with amiodarone

The electrophysiological effects of dronedarone, a new nonionidated analogue of amiodarone were studied after chronic and acute administration in dog Purkinje fibres, papillary muscle and isolated ventricular myocytes, and compared with those of amiodarone by applying conventional microelectrode and...

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Bibliographic Details
Published in:British journal of pharmacology 2001-07, Vol.133 (5), p.625-634
Main Authors: Varró, András, Takács, János, Németh, Miklós, Hála, Ottó, Virág, László, Iost, Norbert, Baláti, Beáta, Ágoston, Márta, Vereckei, András, Pastor, Gilbert, Delbruyère, Martine, Gautier, Patrick, Nisato, Dino, Papp, Julius Gy
Format: Article
Language:English
Subjects:
Action potentials
Action Potentials - drug effects
amiodarone
Amiodarone - analogs & derivatives
Amiodarone - blood
Amiodarone - chemistry
Amiodarone - pharmacology
Animals
Antianginal agents. Coronary vasodilator agents
antiarrhythmic drugs
Biological and medical sciences
Cardiovascular system
Dogs
Dronedarone
Electric Stimulation
Electrocardiography
Electrophysiology
Female
Heart Ventricles - cytology
Heart Ventricles - drug effects
In Vitro Techniques
Male
Medical sciences
Papillary Muscles - drug effects
Papillary Muscles - physiology
Pharmacology. Drug treatments
Purkinje Fibers - drug effects
Purkinje Fibers - physiology
SR 33589
Vasodilator Agents - pharmacology
Ventricular Function
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Summary:The electrophysiological effects of dronedarone, a new nonionidated analogue of amiodarone were studied after chronic and acute administration in dog Purkinje fibres, papillary muscle and isolated ventricular myocytes, and compared with those of amiodarone by applying conventional microelectrode and patch‐clamp techniques. Chronic treatment with dronedarone (2×25 mg−1 kg−1 day p.o. for 4 weeks), unlike chronic administration of amiodarone (50 mg−1 kg−1 day p.o. for 4 weeks), did not lengthen significantly the QTc interval of the electrocardiogram or the action potential duration (APD) in papillary muscle. After chronic oral treatment with dronedarone a small, but significant use‐dependent Vmax block was noticed, while after chronic amiodarone administration a strong use‐dependent Vmax depression was observed. Acute superfusion of dronedarone (10 μM), similar to that of amiodarone (10 μM), moderately lengthened APD in papillary muscle (at 1 Hz from 239.6±5.3 to 248.6±5.3 ms, n=13, P
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0704106