Dronedarone hydrochloride

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) :Dronedarone (SR-33589) is a multichannel blocker for atrial fibrillation . It is a potent inhibitor of the acetylcholine-activated K+ current from atrial and sinoatrial nodal tissue, and inhibits the rapid delayed rectifier more potently than slow and inward rectifier K+ currents and inhibits L-type calcium current. Under whole-cell patch clamp, it blocks IKr (IC50=3 μM) and ICa-L (IC50=0.18 μM) . The effects on ICa-L are use- and frequency-dependent. Dronedarone inhibits current carried by human ether-a-go-go gene (HERG) -expressing oocytes (analagous to IKr) with an IC50 of 9 μM. In guinea pig ventricular myocytes, dronedarone exhibits a state dependent inhibition of the fast Na+ channel current with an IC50 of 0.7±0.1 μM, when the holding potential is 80 mV. (In Vivo) :Dronedarone (Hydrochloride) reduces significantly the incidence of ventricular fibrillation (VF) from 80 to 30% (p < 0.05) at 3 mg/kg i.v. and eliminated VF and mortality at 10 mg/kg i.v. . Dronedarone inhibited carotid artery thrombus formation in vivo. Thrombin- and collagen-induced platelet aggregation is impaired indronedarone-treated mice (P\0.05), and expression ofplasminogen activator inhibitor-1 (PAI1), an inhibitor of the fibrinolytic system, is reduced in the arterial wall.