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

1 The electrophysiological effects of dronedarone, a new nonionidated analo gue of amiodarone were studied after chronic and acute administration in do g Purkinje fibres, papillary muscle and isolated ventricular myocytes, and compared with those of amiodarone by applying conventional microelectrode a nd patch-clamp techniques. 2 Chronic treatment with dronedarone (2 x 25 mg(-1) kg(-1) day p.o. for 4 w eeks), 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 ele ctocardiogram or the action potential duration (APD) in papillary muscle. A fter chronic oral treatment with dronedarone a small, but significant use-d ependent V-max block was noticed, while after chronic amiodarone administra tion a strong use-dependent V-max depression was observed. 3 Acute superfusion of dronedarone (10 muM), similar to that of amiodarone (10 muM), moderately lengthened APD in papillary muscle (at 1 Hz from 239.6 +/- 5.3 to 248.6 +/- 5.3 ms, n=13, P < 0.05), but shortened it in Purkinje fibres (at 1 nz from 309.6 +/- 11.8 to 287.1 +/- 10.8 ms, n=7, P < 0.05). 4 Both dronedarone (10 muM) and amiodarone (10 muM) superfusion reduced the incidence of early and delayed afterdepolarizations evoked by 1 muM dofeti lide and 0.2 muM strophantidine in Purkinje fibres. 5 In patch-clamp experiments 10 muM dronedarone markedly reduced the L-type calcium current (76.5 +/- 10.7 %, n=6, P < 0.05) and the rapid component o f the delayed rectifier potassium current (97 +/- 1.2 %, n=5, P < 0.05) in ventricular myocytes. 6 It is concluded that after acute administration dronedarone exhibits effe cts on cardiac electrical activity similar to those of amiodarone, but it l acks the 'amiodarone like' chronic electrophysiological characteristics.