Amiodarone hydrochloride

Amiodarone hydrochloride Basic information
Product Name:Amiodarone hydrochloride
Synonyms:2-BUTYL-3-BENZOFURANYL 4-[2-(DIETHYLAMINO)ETHOXY]-3,5-DIIODOPHENYL KETONE HYDROCHLORIDE;(2-BUTYL-3-BENZOFURANYL)-[4-[2-(DIETHYLAMINO)ETHOXY]-3,5-DIIODO-PHENYL]-METHANONE HYDROCHLORIDE;AMIODARONE-D4 HCL;AMIODARONE HCL;AMIODARONE HYDROCHLORIDE;AMIODARONUM HYDROCHLORIDE;2-butyl-3-benzofuryl 4-[2-(diethylamino)ethoxy]-3,5-diiodophenyl ketone hydrochloride;AMIODARONEHCL(2-BUTYL-3-BENZOFURANYL-4-[2-(DIETHYLAMINO)ETHOXY]-3,5-DIIODOPHENYLKETONE)
CAS:19774-82-4
MF:C25H29I2NO3.ClH
MW:681.77
EINECS:243-293-2
Product Categories:API;API's;Heterocycles;Intermediates & Fine Chemicals;Pharmaceuticals;Ion transporter and other ion channel;Active Pharmaceutical Ingredients;19774-82-4
Mol File:19774-82-4.mol
Amiodarone hydrochloride Structure
Amiodarone hydrochloride Chemical Properties
Melting point 154-158°C
Fp 9℃
storage temp. 2-8°C
solubility Soluble in chloroform, methanol.
form neat
pkapKa (25°C) 6.56 ±0.06
color White
λmax242nm(MeOH)(lit.)
Merck 14,482
Stability:Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 2 months.
CAS DataBase Reference19774-82-4(CAS DataBase Reference)
Safety Information
Hazard Codes Xn,T,F
Risk Statements 20/21/22-39/23/24/25-23/24/25-11
Safety Statements 36-45-36/37-16-7
RIDADR UN1230 - class 3 - PG 2 - Methanol, solution
WGK Germany 3
RTECS OB1361000
HS Code 29322090
Hazardous Substances Data19774-82-4(Hazardous Substances Data)
Toxicitydog,LD50,intravenous,5gm/kg (5000mg/kg),Iyakuhin Kenkyu. Study of Medical Supplies. Vol. 23, Pg. 682, 1992.
MSDS Information
ProviderLanguage
SigmaAldrich English
Amiodarone hydrochloride Usage And Synthesis
DescriptionAmiodarone HCl (19774-82-4) is a nonselective ion channel blocker. Class III antiarrhythmic.1 Induces cytochrome c release and induces apoptosis.2 An alkalizing agent which stimulates progranulin (GRN) production and prevents GRN-dependent neurodegeneration.3 Induces autophagy and suppresses hepatocellular carcinoma tumorigenesis via autophagy-mediated MIR224 degradation in vitro and in vivo.4
Chemical PropertiesWhite Solid
OriginatorCordarone,Labaz,France,1971
UsesAmiodarone induces an immediate influx of Ca2+ in Saccharomyces cerevisiae, followed by mitochondrial fragmentation and cell death.
UsesAntiarrhythmic;Na+ channel blocker
UsesA non-selective ion channel blocker. Antiarrhythmic (class III)
UsesAmiodarone hydrochloride is a non-selective ion channel blocker with broad fungicidal activity. Amiodarone induces an immediate influx of Ca2+ in Saccharomyces cerevisiae, followed by mitochondrial fragmentation and cell death. Amiodarone hydrochloride has also been used in a study to determine concentrations of thyroid disrupting substances in effluents from wastewater treatment plants.
DefinitionChEBI: Amiodarone hydrochloride is an aromatic ketone.
Manufacturing Process135 grams of 2-n-butyl-3-(3,5-diiodo-4-hydroxybenzoyl)benzofuran dissolved in 600 cc of ethyl carbonate were treated with 5.7 grams of sodium in the form of sodium methoxide in methanol. Then, β-diethylaminoethyl chloride which had been obtained from 51.6 grams of the hydrochloride in ethyl carbonate was introduced into a suspension of the sodium salt. The mixture was heated to a temperature of approximately 90°C which was maintained for approximately 2 hours. The mixture was cooled and allowed to stand overnight during which time the sodium chloride settled down.
The toluene solution containing diethylaminoethyl ether was extracted with increasingly diluted aqueous hydrochloric acid solutions while stirring. Extraction was continued until the alkalized solution produced no further precipitate. The combined aqueous solutions were washed with ether and then made strongly alkaline with aqueous sodium hydroxide. Extraction with ether was carried out three times. The organic layers were washed with water and then dried over anhydrous potassium carbonate. In order to produce the hydrochloride, the carbonate was filtered off and then the hydrochloride was precipitated from the ether solution with an ethereal hydrochloric acid solution. After the solution had been allowed to stand for a few hours, decantation was carried out and the syrupy hydrochloride residue was taken up in 500 cc of boiling acetone. The salt crystallized out by cooling. The substance was allowed to stand overnight at 0°C, and centrifuged, washed with ethyl acetate and then with ether and dried. 130 grams of 2-n-butyl-3- (3,5-diiodo-4-β-N-diethylaminoethoxybenzoyl)benzofuran hydrochloride in the form of a crystalline powder which melts at 156°C were obtained.
Therapeutic FunctionCoronary vasodilator
General DescriptionAmiodarone, marketed as Pacerone?, Cordarone?, Aratac, and Atlansil, is an antiarrhythmic agent monitored by clinical labs using HPLC or LCMS to ensure patients remain within the drugs therapeutic range.
Biochem/physiol ActionsNon-selective ion channel blocker with broad fungicidal activity. Amiodarone induces an immediate influx of Ca2+ in Saccharomyces cerevisiae, followed by mitochondrial fragmentation and cell death.
Clinical UseCardiac arrhythmias
Veterinary Drugs and TreatmentsBecause of its potential toxicity and lack of experience with use in canine and equine patients, amiodarone is usually used when other less toxic or commonly used drugs are ineffective. It may be useful in dogs and horses to convert atrial fib into sinus rhythm and in dogs for arrhythmias associated with left ventricular dysfunction. In horses, one horse with Ventricular tachycardia was converted into sinus rhythm using amiodarone.
As the risk of sudden death is high in Doberman pinschers exhibiting rapid, wide-complex ventricular tachycardia or syncope with recurrent VPC’s, amiodarone may be useful when other drug therapies are ineffective.
Drug interactionsPotentially hazardous interactions with other drugs
Anti-arrhythmics: additive effect and increased risk of myocardial depression; increased risk of ventricular arrhythmias with disopyramide or dronedarone - avoid; increased flecainide concentration - halve flecainide dose; increased procainamide concentration - avoid.
Antibacterials: increased risk of ventricular arrhythmias with parenteral erythromycin, cotrimoxazole levofloxacin and moxifloxacin - avoid; increased risk of ventricular arrhythmias with delamanid; avoid with fidaxomicin; possibly increased risk of ventricular arrhythmias with telithromycin.
Anticoagulants: metabolism inhibited (increased anti-coagulant effect); increased dabigatran concentration (reduce dabigatran dose).
Antidepressants: increased risk of ventricular arrhythmias with citalopram and escitalopram, tricyclic antidepressants and venlafaxine - avoid.
Antiepileptics: phenytoin and fosphenytoin metabolism inhibited (increased concentration).
Antifungals: avoid with fluconazole due to risk of QT prolongation.
Antihistamines: increased risk of ventricular arrhythmias with mizolastine - avoid.
Antimalarials: increased risk of ventricular arrhythmias with chloroquine, hydroxychloroquine, mefloquine and quinine and possibly with piperaquine with artenimol and artemether/ lumefantrine - avoid.
Antimuscarinics: increased risk of ventricular arrhythmias with tolterodine.
Antipsychotics: increased risk of ventricular arrhythmias with antipsychotics that prolong the QT interval; increased risk of ventricular arrhythmias with amisulpride, benperidol, droperidol, haloperidol, phenothiazines, pimozide or zuclopenthixol - avoid; increased risk of ventricular arrhythmias with sulpiride.
Antivirals: increased risk of ventricular arrhythmias with fosamprenavir ritonavir, saquinavir and telaprevir - avoid; concentration possibly increased by atazanavir; possible increased risk of bradycardia with daclatasvir, ledipasvir, sofosbuvir and simeprevir; avoid with indinavir, reduce the dose of the others.
Atomoxetine: increased risk of ventricular arrhythmias.
Beta-blockers, diltiazem, and verapamil: increased risk of bradycardia, AV block and myocardial depression; increased risk of ventricular arrhythmias with sotalol - avoid.
Ciclosporin: increased levels of ciclosporin possible.
Cobicistat: concentration possibly increased by cobicistat - avoid.
Colchicine: possibly increased colchicine toxicity.
Cytotoxics: possibly increased afatinib concentration (separate administration by 6-12 hours); possibly increased risk of ventricular arrhythmias with panobinostat and vandetanib - avoid; concentration of ibrutinib possibly increased - reduce dose of ibrutinib; avoid with idelalisib; increased risk of ventricular arrhythmias with arsenic trioxide, bosutinib and ceritinib.
Digoxin: increased concentration (halve digoxin maintenance dose).
Fingolimod: possible increased risk of bradycardia.
Grapefruit juice: may increase concentration of amiodarone - avoid.
Ivabradine: increased risk of ventricular arrhythmias - avoid.
Lipid-lowering drugs: give lomitapide 12 hours after amiodarone; increased risk of myopathy with simvastatin - do not exceed 20 mg of simvastatin.1 Lithium: increased risk of ventricular arrhythmias - avoid.
Pentamidine: increased risk of ventricular arrhythmias - avoid.







MetabolismAmiodarone is metabolised in the liver; the major metabolite, desethylamiodarone, also has antiarrhythmic properties. There is very little urinary excretion of amiodarone or its metabolites, the major route of excretion being in faeces via the bile; some enterohepatic recycling may occur.
storageStore at +4°C
References1) Yamase et al. (2012), Effectiveness of amiodarone versus bepridil in achieving conversion to sinus rhythm in patients with persistent atrial fibrillation: a randomized trial; Heart, 98 1067 2) Di Matola et al. (2000), Amiodarone induces cytochrome c release and apoptosis through an iodine-independent mechanism; J. Clin. Endocrinol. Metab., 85 4323 3) Capell et al. (2011), Rescue of progranulin deficiency associated with frontotemporal lobar degeneration by alkalizing reagents and inhibition of vacuolar ATPase; J. Neurosci., 31 1885 4) Lan et al. (2014), Autophagy-preferential degradation of MIR224 participates in hepatocellular carcinoma tumorigenesis; Autophagy, 10 1687
Ethyl vinyl ether Cyhalofop-butyl Sibutramine hydrochloride DIETHOXYMETHANE Buprofezin Ethoxyquin Amiodarone Diethylene glycol monobutyl ether Butyl acrylate Butyl acetate 2-Ethoxyethanol Ethoxy 1-AdaMantanethylaMine Amiodarone hydrochloride tert-Butylchlorodiphenylsilane 2-Butoxyethanol Ethoxyethyne tert-Butylhydrazine hydrochloride

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