Dronedarone

A multichannel blocker agent that has antiarrhythmic activity; reduces the late sustained K (+) current, I (K) (or Isus) with EC50 of 0.85 uM in postmyocardial infarcted (PMI) rats; reduces significantly the incidence of ventricular fibrillation (VF) in rats; mainly used for treatment of cardiac arrhythmias.Heart Arrhythmia Approved (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.In guinea pig ventricular myocytes, Dronedarone inhibits the rapidly activating delayed-rectifier potassium current (IC5030 μM), and L-type calcium current (IC50=0.18 μM) .Dronedarone exhibits strong inhibitory effects on the acetylcholine-activated potassium current (IK-Ach) in rabbit inoatrial nodal cells (IC50=63 nM) and guinea pig atrial cells (IC50=10 nM) . Blockade of IK-Ach by dronedarone is 100 times more potent than that of amiodarone.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.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. (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.