Disease relevance of Dronedarone

• Dronedarone for prevention of atrial fibrillation: a dose-ranging study [1].
• CONCLUSION: Dronedarone, at a 800 mg daily dose, appears to be effective and safe for the prevention of AF relapses after cardioversion [1].
• We studied the effects of dronedarone (SR 33589) on the action potentials, membrane ionic currents, and arrhythmic activity in control rats and in rats after myocardial infarction, a model known to develop anomalous electrical activity [2].
• On rats, which after myocardial infarction exhibited ventricular premature beats, dronedarone significantly decreased beat occurrence during the 7-day treatment; this effect was sustained for two more weeks [2].
• Effect of Dronedarone on Cardiac Na Current. INTRODUCTION: Amiodarone (AM) is a highly effective antiarrhythmic agent used in the management of both atrial and ventricular arrhythmias [3].

High impact information on Dronedarone

• Pump current was also measured in myocytes isolated from a separate group of rabbits not subjected to thyroidectomy but treated with dronedarone, or placebo for 3 weeks [4].
• Chronic amiodarone-induced inhibition of the Na+-K+ pump in rabbit cardiac myocytes is thyroid-dependent: comparison with dronedarone [4].
• Dronedarone blocked HERG channels with an IC50 value of 9.2 microM and a maximum tail current reduction of 85.2% [5].
• Dronedarone exhibited a weaker block of KvLQT1/minK currents (33.2% at 100 microM drug concentration), without causing significant changes in the corresponding current-voltage relationships [5].
• Dronedarone increased action potential duration in normal hearts [2].

Chemical compound and disease context of Dronedarone

• Additionally, in patients with permanent AF, dronedarone was highly effective at controlling ventricular rate on top of standard rate-controlling therapies in the Efficacy and Safety of Dronedarone for the Control of Ventricular Rate during Atrial Fibrillation (ERATO) study [6].
• Amiodarone (30 mg/kg/day per os) or dronedarone (30 mg/kg/day per os) were administered for 2 weeks in normal and thyroxine-treated animals (25 microg/100 g body weight od sc, for 2 weeks), while animals without amiodarone and dronedarone served as controls [7].
• Further trials are also needed to discover more favorable compounds with multiple receptors including I(Kr) (e.g. nifekalant, dronedarone) for treating ventricular arrhythmias [8].

Biological context of Dronedarone

• Involvement of nitric oxide in amiodarone- and dronedarone-induced coronary vasodilation in guinea pig heart [9].
• Thus, dronedarone and amiodarone displayed a similar level of antiadrenergic effect and did not impair the resting left ventricular function [10].
• Our data demonstrate that the acute electrophysiological characteristics of dronedarone, despite absence of iodine in its molecular structure, are very similar to those of amiodarone in cardiac ventricle [11].
• In multicellular preparations, dronedarone (3, 10, and 30 microM) decreased maximum rate of rise of AP (dV/dt max) with a concentration- and frequency-dependent relationship; resting potential was not modified and AP amplitude was decreased only at 30 microM [11].
• Herein, we show that pharmacological inhibition of TRalpha1 by dronedarone, an amiodarone like compound (shown to antagonize thyroid hormone binding to TRalpha1), prevented the thyroid hormone induced increase in food intake and heart rate acceleration in rats [12].

Anatomical context of Dronedarone

• 1. The effect of the antiarrhythmic drug dronedarone on the Acetylcholine-activated K(+) current (I(K(ACh))) was investigated in single cells isolated from sinoatrial node (SAN) tissue of rabbit hearts [13].
• Effects of dronedarone and amiodarone on plasma thyroid hormones and on the basal and postischemic performance of the isolated rat heart [7].
• Simultaneously to these electrophysiological effects, dronedarone reduced contraction amplitudes of papillary muscle and decreased Ca2+ transient and shortening of ventricular myocytes [11].
• Deiodination and other structural changes in the amiodarone molecule have has led to a the loss of thyroid and pulmonary effects in the resulting derivative, dronedarone, which is in advanced clinical development [14].

Associations of Dronedarone with other chemical compounds

• Cmax and AUC0--24 h of metoprolol increased from days 5 to 13 in proportion to dronedarone dose only in CYP2D6 extensive metabolizers genotyped subjects (P < 0.001) [15].

Analytical, diagnostic and therapeutic context of Dronedarone

• This study was designed to determine the most appropriate dose of dronedarone for prevention of atrial fibrillation (AF) after cardioversion [1].
• 4. External cell perfusion with dronedarone inhibited the activity of I(K(ACh)) channels recorded from cell-attached patches by reducing the channel open probability (from 0.56 to 0.11) without modification of the single-channel conductance [13].
• Holter monitoring study in control, unthetered animals showed that dronedarone had no proarrhythmic effect [2].
• 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 [16].
• Like amiodarone and dronedarone, its efficiency in these animal models of arrhythmias is likely be related to its multifactorial mechanism of action [17].

References