tcsc0712 Dronedarone (Hydrochloride)

Dronedarone hydrochloride is a non-iodinated amiodarone derivative that inhibits Na⁺, K⁺ and Ca²⁺ currents.

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 I_Kr (IC₅₀=3 μM) and I_Ca-L (IC₅₀=0.18 μM). The effects on I_Ca-L are use- and frequency-dependent. Dronedarone inhibits current carried by human ether-a-go-go gene (HERG)-expressing oocytes (analagous to I_Kr) with an IC₅₀ of 9 μM^[1]. 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^[2].

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. ^[3]. 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^[4].