Dronedarone

Dronedarone (SR 33589), a derivative of amiodarone (HY-14187), is a class III antiarrhythmic agent for the study of atrial fibrillation (AF) and atrial flutter. Dronedarone is a potent blocker of multiple ion currents, including potassium current, sodium current, and L-type calcium current, and exhibits antiadrenergic effects by noncompetitive binding to β-adrenergic receptors. Dronedarone is a substrate for and a moderate inhibitor of CYP3A4^[1]. In Vitro:In patch clamp experiments using human atrial myocytes, Dronedarone produces potent blockade of peak sodium current, resulting in a 97% block at 3 μM^[1].
In guinea pig ventricular myocytes, Dronedarone inhibits the rapidly activating delayed-rectifier potassium current (IC₅₀<3 μM), the slowly activating delayed-rectifier potassium current (IC₅₀=10 μM), the inward rectifier potassium current (IC₅₀>30 μM), and L-type calcium current (IC₅₀=0.18 μM)^[1].
Dronedarone exhibits strong inhibitory effects on the acetylcholine-activated potassium current (I_K-Ach) in rabbit inoatrial nodal cells (IC₅₀=63 nM) and guinea pig atrial cells (IC₅₀=10 nM). Blockade of I_K-Ach by dronedarone is 100 times more potent than that of amiodarone^[1].
Dronedarone exerts its antiadrenergic effects by noncompetitive binding to β-adrenergic receptors (IC₅₀=1.8 μM) and inhibition of agonist-induced increases in adenylate cyclase activity^[1].
Dronedarone (0.01-1 μM) induces a concentration-dependent reduction of coronary perfusion pressure in isolated guinea pig hearts, effects that are independent of the nitric oxide synthase pathway and possibly related to its calcium current blockade^[1].
In Vivo:Dronedarone (intraperitoneal injection; 25-100 mg/kg) exhibits anticonvulsant effects in a dose-dependent manner and increases the threshold for electroconvulsions in mice^[2].