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Dronedarone
Dronedarone
ChemFaces products have been cited in many studies from excellent and top scientific journals
Product Name Dronedarone
Price: $218 / 20mg
CAS No.: 141626-36-0
Catalog No.: CFN90014
Molecular Formula: C31H44N2O5S
Molecular Weight: 556.76 g/mol
Purity: >=98%
Type of Compound: Alkaloids
Physical Desc.: Powder
Source: From Streptomycetaceae
Solvent: Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.
Download: COA    MSDS    SDF
Similar structural: Comparison (Web)  (SDF)
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According to end customer requirements, ChemFaces provide solvent format. This solvent format of product intended use: Signaling Inhibitors, Biological activities or Pharmacological activities.
Size /Price /Stock 10 mM * 1 mL in DMSO / $102.0 / In-stock
Other Packaging *Packaging according to customer requirements(100uL/well, 200uL/well and more), and Container use Storage Tube With Screw Cap
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Related Screening Libraries
Size /Price /Stock 10 mM * 100 uL in DMSO / Inquiry / In-stock
10 mM * 1 mL in DMSO / Inquiry / In-stock
Related Libraries
Biological Activity
Description: Dronedarone is a derivative of amiodarone which is classified as a Class III antiarrhythmic agent. It shows rate-dependent inhibition of the rapid Na+ current, inhibits α and β-adrenergic receptors like Class II agents, exhibits blockade of K+ outward currents as the main mechanism of action of Class III, and effectively block slow Ca2+ inward currents (Class IV).
Targets: Calcium Channel | Sodium Channel | Potassium Channel
In vivo:
Expert Opin Drug Saf. 2015 Jun;14(6):807-13.
Dronedarone and renal impairment: evaluation of Spanish postmarketing reports and review of literature.[Pubmed: 25967281]
Renal impairment associated with Dronedarone use is hardly known. Our aim is to describe the characteristics of spontaneous reports involving renal adverse reactions with use of Dronedarone.
METHODS AND RESULTS:
In the Spanish Pharmacovigilance database, reports with renal reactions and Dronedarone until May 2014 were retrieved and analyzed. Also, a review of case reports of renal failure and Dronedarone was conducted in MEDLINE. Dronedarone was found as a suspected drug in 192 reports, 10 (5.2%) of these reports described renal reactions. Renal reactions appeared until 3 months after the onset of Dronedarone treatment. In 5 out of 10 cases, Dronedarone was withdrawn and the patient recovered. The Reporting Odds Ratio was 2.88 [95% CI 1.52 - 5.46; p < 0.05]. Additionally, eight cases were found in the medical literature. In five of them, the patient outcome was described as recovered. One patient had to undergo hemodialysis for the treatment of their renal impairment.
CONCLUSIONS:
The effect of Dronedarone on the renal function is supported by limited information; therefore, the cases from spontaneous reporting system and those from the medical literature could give relevant additional information. Our analysis shows a potential relationship between Dronedarone use and renal impairment. Further studies are needed to confirm these findings.
Curr Cardiol Rev. 2014 Nov;10(4):303-8.
The role of dronedarone in the treatment of atrial fibrillation/flutter in the aftermath of PALLAS.[Pubmed: 24821656]
Dronedarone is an amiodarone analog that differs structurally from amiodarone in that the iodine moiety was removed and a methane-sulfonyl group was added. These modifications reduce thyroid and other end-organ adverse effects and makes Dronedarone less lipophilic, with a shorter half-life.
METHODS AND RESULTS:
Dronedarone has been shown to prevent atrial fibrillation/ flutter (AF/AFl) recurrences in several multi-center trials. In addition to its rhythm control properties, Dronedarone has rate control properties. In patients with decompensated heart failure, Dronedarone treatment increased mortality and cardiovascular hospitalizations. When Dronedarone was used in elderly high risk AF/AFl patients, excluding those with advanced heart failure, cardiovascular hospitalizations were significantly reduced. The results of the PALLAS trial suggest that Dronedarone should not be used in the long-term treatment of patients with permanent AF.
CONCLUSIONS:
Post-marketing data have demonstrated rare hepatic toxicity to be associated with Dronedarone use.Updated practice and regulatory guidelines have positioned Dronedarone as a front-line antiarrhythmic in many patients with AF/Fl. However, the drug should not be used in patients with advanced heart failure and in patients who develop permanent AF.
J Interv Card Electrophysiol. 2015 Mar;42(2):69-76.
A placebo-controlled, double-blind, randomized, multicenter study to assess the effects of dronedarone 400 mg twice daily for 12 weeks on atrial fibrillation burden in subjects with permanent pacemakers.[Pubmed: 25638303]
Dronedarone is a benzofuran derivative with a pharmacological profile similar to amiodarone but has a more rapid onset of action and a much shorter half-life (13-19 h). Our goal was to evaluate the efficacy of Dronedarone in atrial fibrillation (AF) patients using dual-chamber pacemakers capable of quantifying atrial fibrillation burden.
METHODS AND RESULTS:
Pacemakers were adjusted to optimize AF detection. Patients with AF burden >1% were randomized to Dronedarone 400 mg twice daily (BID) or placebo. Pacemakers were interrogated after 4 and 12 weeks of treatment. The primary endpoint was the change in AF burden from baseline over the 12-week treatment period. Patients with permanent AF, severe/recently decompensated heart failure, and current use of antiarrhythmic drugs were excluded. AF burden was assessed by a core laboratory blinded to treatment assignment. From 285 patients screened, 112 were randomized (mean age 76 years, 60% male, 84% hypertensive, 65% with sick sinus syndrome, 26% with diabetes mellitus type II, 15% with heart failure). Baseline mean (SEM) AF burden was 8.77% (0.16) for placebo and 10.14% (0.17) for Dronedarone. Over the 12-week study period, AF burden compared to baseline decreased by 54.4% (0.22) (P = 0.0009) with Dronedarone and trended higher by 12.8% (0.16) (P = 0.450) with placebo. The absolute change in burden was decreased by 5.5% in the Dronedarone group and increased by 1.1% in the placebo group. Heart rate during AF was reduced to approximately 4 beats/min with Dronedarone (P = 0.285). Adverse events were higher with Dronedarone compared to placebo (65 vs 56%).
CONCLUSIONS:
Dronedarone reduced pacemaker-assessed the relative AF burden compared to baseline and placebo by over 50% during the 12-week observation period.
Dronedarone Description
Source: From Streptomycetaceae
Solvent: Chloroform, Dichloromethane, Ethyl Acetate, DMSO, Acetone, etc.
Storage: Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months(2-8C).

Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20C. Generally, these will be useable for up to two weeks. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour.

Need more advice on solubility, usage and handling? Please email to: service@chemfaces.com

After receiving: The packaging of the product may have turned upside down during transportation, resulting in the natural compounds adhering to the neck or cap of the vial. take the vial out of its packaging and gently shake to let the compounds fall to the bottom of the vial. for liquid products, centrifuge at 200-500 RPM to gather the liquid at the bottom of the vial. try to avoid loss or contamination during handling.
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Calculate Dilution Ratios(Only for Reference)
1 mg 5 mg 10 mg 20 mg 25 mg
1 mM 1.7961 mL 8.9805 mL 17.9611 mL 35.9221 mL 44.9027 mL
5 mM 0.3592 mL 1.7961 mL 3.5922 mL 7.1844 mL 8.9805 mL
10 mM 0.1796 mL 0.8981 mL 1.7961 mL 3.5922 mL 4.4903 mL
50 mM 0.0359 mL 0.1796 mL 0.3592 mL 0.7184 mL 0.8981 mL
100 mM 0.018 mL 0.0898 mL 0.1796 mL 0.3592 mL 0.449 mL
* Note: If you are in the process of experiment, it's need to make the dilution ratios of the samples. The dilution data of the sheet for your reference. Normally, it's can get a better solubility within lower of Concentrations.
Protocol
Animal Research:
Toxicology. 2014 Sep 2;323:1-9.
Hepatic toxicity of dronedarone in mice: role of mitochondrial β-oxidation.[Pubmed: 24881592]
Dronedarone is an amiodarone-like antiarrhythmic drug associated with severe liver injury. Since Dronedarone inhibits mitochondrial respiration and β-oxidation in vitro, mitochondrial toxicity may also explain Dronedarone-associated hepatotoxicity in vivo.
METHODS AND RESULTS:
We therefore studied hepatotoxicity of Dronedarone (200mg/kg/day for 2 weeks or 400mg/kg/day for 1 week by intragastric gavage) in heterozygous juvenile visceral steatosis (jvs(+/-)) and wild-type mice. Jvs(+/-) mice have reduced carnitine stores and are sensitive for mitochondrial β-oxidation inhibitors. Treatment with Dronedarone 200mg/kg/day had no effect on body weight, serum transaminases and bilirubin, and hepatic mitochondrial function in both wild-type and jvs(+/-) mice. In contrast, Dronedarone 400mg/kg/day was associated with a 10-15% drop in body weight, and a 3-5-fold increase in transaminases and bilirubin in wild-type mice and, more accentuated, in jvs(+/-) mice. In vivo metabolism of intraperitoneal (14)C-palmitate was impaired in wild-type, and, more accentuated, in jvs(+/-) mice treated with 400mg/kg/day Dronedarone compared to vehicle-treated mice. Impaired β-oxidation was also found in isolated mitochondria ex vivo. A likely explanation for these findings was a reduced activity of carnitine palmitoyltransferase 1a in liver mitochondria from Dronedarone-treated mice. In contrast, Dronedarone did not affect the activity of the respiratory chain ex vivo. We conclude that Dronedarone inhibits mitochondrial β-oxidation in and ex vivo, but not the respiratory chain. Jvs(+/-) mice are slightly more sensitive for the effect of Dronedarone on mitochondrial β-oxidation than wild-type mice.
CONCLUSIONS:
The results suggest that inhibition of mitochondrial β-oxidation is an important mechanism of hepatotoxicity associated with Dronedarone.
Europace. 2015 Feb 20. pii: euu393.
Dronedarone and digitalis: individually reduced post-repolarization refractoriness enhances life-threatening arrhythmias.[Pubmed: 25713011 ]
Interaction between Dronedarone and digitalis has been discussed as a possible cause for increased mortality in the presence of Dronedarone observed in the PALLAS trial. The aim of this study was to assess possible proarrhythmic effects of Dronedarone in combination with digitalis in an experimental whole heart model.
METHODS AND RESULTS:
Twenty-six female rabbits underwent chronic oral treatment with Dronedarone (50 mg/kg/day for 6 weeks). Twenty-four rabbits received placebo. Heart failure was induced by rapid ventricular pacing. Sham-operated rabbits received a right-ventricular pacing lead but were not paced. Thereafter, hearts were isolated and Langendorff-perfused. Monophasic action potentials and a 12 lead electrocardiogram showed a dose-dependent decrease of QT interval, APD90, effective refractory periods, and postrepolarization refractoriness in control hearts and Dronedarone-pretreated hearts after application of ouabain (0.1 and 0.2 µM). After acute application of ouabain, ventricular fibrillation (VF) was inducible by programmed ventricular stimulation in 6 of 12 untreated sham hearts (38 episodes) as compared with 7 of 11 Dronedarone-pretreated sham hearts (76 episodes). In untreated failing hearts, 6 of 12 hearts were inducible (47 episodes) as compared with 7 of 15 hearts Dronedarone-pretreated failing hearts (93 episodes).
CONCLUSIONS:
In this study, ouabain treatment resulted in an increased ventricular vulnerability in chronically Dronedarone-pretreated control and failing hearts. Ouabain led to a significant abbreviation of ventricular repolarization. This was more marked in Dronedarone-pretreated hearts and resulted in an elevated incidence of VF. This may help to interpret the results of the PALLAS trial.
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