Dronedarone

SKU: orb1226331

Description

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.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 141626-36-0
• MW: 556.7565
• Purity: >98% (HPLC)
• Formula: C₃₁H₄₄N₂O₅S
• SMILES: CS(=O)(NC1=CC2=C(OC(CCCC)=C2C(C3=CC=C(OCCCN(CCCC)CCCC)C=C3)=O)C=C1)=O
• Target: Potassium Channel
• Solubility: 10 mM in DMSO

Bioactivity

• 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. Animal model: Tonic-clonic seizures in male albino Swiss outbred mice. Dosage: 25 mg/kg; 50 mg/kg; 75 mg/kg; 100 mg/kg. Administration: Intraperitoneal injection. Result: Showed significant anticonvulsant effects.
• 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 (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). 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.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

SR-33589

Quick Database Links

Gene Symbol

Potassium Channel