Dronedarone hydrochloride

Names

[ Name ]:
Dronedarone hydrochloride

[Synonym ]:
n-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)-5-benzofuranyl)methanesulfonamide monohydrochloride
N-(2-Butyl-3-{4-[3-(dibutylamino)propoxy]benzoyl}-1-benzofuran-5-yl)methanesulfonamide hydrochloride (1:1)
Methanesulfonamide, N-[2-butyl-3-[4-[3-(dibutylamino)propoxy]benzoyl]-5-benzofuranyl]-, hydrochloride (1:1)
Multaq Hydrochloride.
Methanesulfonamide, N-(2-butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)-5-benzofuranyl)-, monohydrochloride
Multaq
Dronedarone (Hydrochloride)
Dronedarone hydrochloride
Dronedarone HCl

Biological Activity

[Description]:

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

[Related Catalog]:

Signaling Pathways >> Autophagy >> Autophagy

Signaling Pathways >> Membrane Transporter/Ion Channel >> Potassium Channel

Research Areas >> Cardiovascular Disease

[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[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].

[Animal admin]

Rats: Rats are anesthetized, artificially ventilated, and the thorax opened by a left thoracotomy. Ischemia is induced by left coronary artery ligation, and reperfusion is achieved (after a 5-min period of ischemia) in a separate group of rats by removing the ligature. Agents are given intravenously 5 min before occlusion or orally 4 h before study[3]. Mice: Twelve-week-old C57Bl/6 mice are divided into two groups: dronedarone (200 mg/kg body weight with a once daily oral gavage for 14 days) or control (1.4 % methylcellulose). Twenty-four hours after the last application, mice are anesthetized by intraperitoneal injection of 87 mg/kg sodium pentobarbital. Rose bengal is diluted to 12 mg/mL in phosphate-buffered saline and then injected into the tail vein at a concentration of 63 mg/kg[4].

[References]

[1]. Bogdan R, et al. Effect of?dronedarone?on Na+, Ca2+ and HCN channels. Naunyn Schmiedebergs Arch Pharmacol.?2011 Apr;383(4):347-56.?

[2]. Doggrell SA, et al. Dronedarone: an amiodarone analogue. Expert Opin Investig Drugs. 2004 Apr;13(4):415-26.

[3]. Manning AS, et al. SR 33589, a new amiodarone-like agent: effect on ischemia- and reperfusion-induced arrhythmias in anesthetized rats. J Cardiovasc Pharmacol. 1995 Sep;26(3):453-61.

[4]. Breitenstein A, et al. Dronedarone reduces arterial thrombus formation. Basic Res Cardiol. 2012 Nov;107(6):302.

[Related Small Molecules]

Chemical & Physical Properties

[ Boiling Point ]:
683.9ºC at 760mmHg

[ Melting Point ]:
NA (low-melting)

[ Molecular Formula ]:
C₃₁H₄₅ClN₂O₅S

[ Molecular Weight ]:
593.217

[ Flash Point ]:
367.4ºC

[ Exact Mass ]:
592.273743

[ PSA ]:
97.23000

[ LogP ]:
9.00480

[ Appearance of Characters ]:
white to off-white

[ Vapour Pressure ]:
1.47E-18mmHg at 25°C

[ Storage condition ]:
Refrigerator

[ Water Solubility ]:
DMSO: soluble15mg/mL, clear

Safety Information

[ RIDADR ]:
UN 3077 9 / PGIII

Articles

Use of In Vitro Morphogenesis of Mouse Embryoid Bodies to Assess Developmental Toxicity of Therapeutic Drugs Contraindicated in Pregnancy.

Toxicol. Sci. 149 , 15-30, (2016)

In utero exposure to certain chemicals can impair embryo development, causing embryonic death, growth retardation, or severe birth defects. Establishment of effective in vitro tests is crucial for ide...

Inactivation of Human Cytochrome P450 3A4 and 3A5 by Dronedarone and N-Desbutyl Dronedarone.

Mol. Pharmacol. 89 , 1-13, (2015)

Dronedarone is an antiarrhythmic agent approved in 2009 for the treatment of atrial fibrillation. An in-house preliminary study demonstrated that dronedarone inhibits cytochrome P450 (CYP) 3A4 and 3A5...