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Record Information
Version2.0
Creation Date2014-09-11 05:14:06 UTC
Update Date2014-12-24 20:26:56 UTC
Accession NumberT3D4737
Identification
Common NameAmiodarone
ClassSmall Molecule
DescriptionAn antianginal and antiarrhythmic drug. It increases the duration of ventricular and atrial muscle action by inhibiting Na,K-activated myocardial adenosine triphosphatase. There is a resulting decrease in heart rate and in vascular resistance.
Compound Type
  • Amine
  • Anti-Arrhythmia Agent
  • Drug
  • Enzyme Inhibitor
  • Ester
  • Ether
  • Organic Compound
  • Synthetic Compound
  • Vasodilator Agent
Chemical Structure
Thumb
Synonyms
Synonym
2-Butyl-3-(3,5-diiodo-4-(2-diethylaminoethoxy)benzoyl)benzofuran
2-Butyl-3-benzofuranyl 4-(2-(diethylamino)ethoxy)-3,5-diiodophenyl ketone
2-N-Butyl-3',5'-diiodo-4'-N-diethylaminoethoxy-3-benzoylbenzofuran
Amio-Aqueous IV
Amiodarona
Amiodaronum
Aratac
Arycor
Atlansil
Cordarone
Nexterone
Pacerone
Tachyra
Chemical FormulaC25H29I2NO3
Average Molecular Mass645.312 g/mol
Monoisotopic Mass645.024 g/mol
CAS Registry Number1951-25-3
IUPAC Name{2-[4-(2-butyl-1-benzofuran-3-carbonyl)-2,6-diiodophenoxy]ethyl}diethylamine
Traditional Nameamiodarone
SMILESCCCCC1=C(C(=O)C2=CC(I)=C(OCCN(CC)CC)C(I)=C2)C2=CC=CC=C2O1
InChI IdentifierInChI=1S/C25H29I2NO3/c1-4-7-11-22-23(18-10-8-9-12-21(18)31-22)24(29)17-15-19(26)25(20(27)16-17)30-14-13-28(5-2)6-3/h8-10,12,15-16H,4-7,11,13-14H2,1-3H3
InChI KeyInChIKey=IYIKLHRQXLHMJQ-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as aryl-phenylketones. These are aromatic compounds containing a ketone substituted by one aryl group, and a phenyl group.
KingdomOrganic compounds
Super ClassOrganic oxygen compounds
ClassOrganooxygen compounds
Sub ClassCarbonyl compounds
Direct ParentAryl-phenylketones
Alternative Parents
Substituents
  • Aryl-phenylketone
  • Benzofuran
  • Phenol ether
  • 3-aroylfuran
  • Benzoyl
  • Phenoxy compound
  • Alkyl aryl ether
  • Halobenzene
  • Iodobenzene
  • Benzenoid
  • Monocyclic benzene moiety
  • Aryl iodide
  • Aryl halide
  • Heteroaromatic compound
  • Furan
  • Tertiary aliphatic amine
  • Tertiary amine
  • Oxacycle
  • Organoheterocyclic compound
  • Ether
  • Amine
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organopnictogen compound
  • Organonitrogen compound
  • Organoiodide
  • Organohalogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
ApplicationsNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point156°C
Boiling PointNot Available
SolubilityLow
LogP7.57
Predicted Properties
PropertyValueSource
Water Solubility0.0048 g/LALOGPS
logP7.24ALOGPS
logP7.64ChemAxon
logS-5.1ALOGPS
pKa (Strongest Basic)8.47ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area42.68 ŲChemAxon
Rotatable Bond Count11ChemAxon
Refractivity145.05 m³·mol⁻¹ChemAxon
Polarizability56.78 ųChemAxon
Number of Rings3ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-000i-9000024000-088b6534d1659c5c174dJSpectraViewer
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-004r-0690000000-25202a61d19d3dfaed8bJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-0000009000-8cbab89986761a7a1bc9JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0pbj-9300003000-503a542bf1a7678f385eJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a4i-9110000000-543b8de3c9ba390fa765JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0udi-0791000000-77d5d18989052c45b006JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0a59-0980000000-a77e32d189cf8e2acdf1JSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0apl-0940000000-30e016c113387b37ca7cJSpectraViewer | MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0002-0000009000-e87a9a6e983c00161bebJSpectraViewer | MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-1200419000-3080963b2267302d337aJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0udi-6920532000-f1048ae0af01f6658877JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-006x-7309200000-46ba6e78349f4d182fe7JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0006-1100029000-9b580022f60608cc2810JSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-006x-3202296000-a7445663ea627302ddceJSpectraViewer
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00di-7902160000-4817e1c5fca0d177a829JSpectraViewer
MSMass Spectrum (Electron Ionization)splash10-000i-9000024000-088b6534d1659c5c174dJSpectraViewer | MoNA
Toxicity Profile
Route of ExposureSlow and variable (about 20 to 55% of an oral dose is absorbed).
Mechanism of ToxicityThe antiarrhythmic effect of amiodarone may be due to at least two major actions. It prolongs the myocardial cell-action potential (phase 3) duration and refractory period and acts as a noncompetitive a- and b-adrenergic inhibitor.
MetabolismAmiodarone is extensively metabolized in the liver via CYP2C8 (under 1% unchanged in urine), and can effect the metabolism of numerous other drugs. The major metabolite of amiodarone is desethylamiodarone (DEA), which also has antiarrhythmic properties. The metabolism of amiodarone is inhibited by grapefruit juice, leading to elevated serum levels of amiodarone. Route of Elimination: Amiodarone is eliminated primarily by hepatic metabolism and biliary excretion and there is negligible excretion of amiodarone or DEA in urine. Half Life: 58 days (range 15-142 days)
Toxicity ValuesIntravenous, mouse: LD50 = 178 mg/kg.
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesIntravenously, for initiation of treatment and prophylaxis of frequently recurring ventricular fibrillation and hemodynamically unstable ventricular tachycardia in patients refractory to other therapy. Orally, for the treatment of life-threatening recurrent ventricular arrhythmias such as recurrent ventricular fibrillation and recurrent hemodynamically unstable ventricular tachycardia.
Minimum Risk LevelNot Available
Health EffectsSome side effects have a significant mortality rate: specifically, hepatitis, exacerbation of asthma and congestive failure, and pneumonitis.
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB01118
HMDB IDNot Available
PubChem Compound ID2157
ChEMBL IDCHEMBL633
ChemSpider ID2072
KEGG IDC06823
UniProt IDNot Available
OMIM ID
ChEBI ID2663
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkAmiodarone
References
Synthesis Reference

DrugSyn.org

MSDST3D4737.pdf
General References
  1. DELTOUR G, BINON F, TONDEUR R, GOLDENBERG C, HENAUX F, SION R, DERAY E, CHARLIER R: [Studies in the benzofuran series. VI. Coronary-dilating activity of alkylated and aminoalkylated derivatives of 3-benzoylbenzofuran]. Arch Int Pharmacodyn Ther. 1962 Sep 1;139:247-54. [14026835 ]
  2. CHARLIER R, DELTOUR G, TONDEUR R, BINON F: [Studies in the benzofuran series. VII. Preliminary pharmacological study of 2-butyl-3-(3,5-diiodo-4-beta-N-diethylaminoethoxybenzoyl)-benzofuran]. Arch Int Pharmacodyn Ther. 1962 Sep 1;139:255-64. [14020244 ]
  3. Singh BN, Vaughan Williams EM: The effect of amiodarone, a new anti-anginal drug, on cardiac muscle. Br J Pharmacol. 1970 Aug;39(4):657-67. [5485142 ]
  4. Rosenbaum MB, Chiale PA, Halpern MS, Nau GJ, Przybylski J, Levi RJ, Lazzari JO, Elizari MV: Clinical efficacy of amiodarone as an antiarrhythmic agent. Am J Cardiol. 1976 Dec;38(7):934-44. [793369 ]
  5. Rosenbaum MB, Chiale PA, Haedo A, Lazzari JO, Elizari MV: Ten years of experience with amiodarone. Am Heart J. 1983 Oct;106(4 Pt 2):957-64. [6613843 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Voltage-gated potassium channel activity involved in ventricular cardiac muscle cell action potential repolarization
Specific Function:
Pore-forming (alpha) subunit of voltage-gated inwardly rectifying potassium channel. Channel properties are modulated by cAMP and subunit assembly. Mediates the rapidly activating component of the delayed rectifying potassium current in heart (IKr). Isoforms USO have no channel activity by themself, but modulates channel characteristics by forming heterotetramers with other isoforms which are retained intracellularly and undergo ubiquitin-dependent degradation.
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular Weight:
126653.52 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Wang SP, Wang JA, Luo RH, Cui WY, Wang H: Potassium channel currents in rat mesenchymal stem cells and their possible roles in cell proliferation. Clin Exp Pharmacol Physiol. 2008 Sep;35(9):1077-84. doi: 10.1111/j.1440-1681.2008.04964.x. Epub 2008 May 25. [18505444 ]
  3. Varro A, Biliczki P, Iost N, Virag L, Hala O, Kovacs P, Matyus P, Papp JG: Theoretical possibilities for the development of novel antiarrhythmic drugs. Curr Med Chem. 2004 Jan;11(1):1-11. [14754422 ]
  4. Waldhauser KM, Brecht K, Hebeisen S, Ha HR, Konrad D, Bur D, Krahenbuhl S: Interaction with the hERG channel and cytotoxicity of amiodarone and amiodarone analogues. Br J Pharmacol. 2008 Oct;155(4):585-95. doi: 10.1038/bjp.2008.287. Epub 2008 Jul 7. [18604229 ]
General Function:
Scaffold protein binding
Specific Function:
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1H gives rise to T-type calcium currents. T-type calcium channels belong to the "low-voltage activated (LVA)" group and are strongly blocked by nickel and mibefradil. A particularity of this type of channels is an opening at quite negative potentials, and a voltage-dependent inactivation. T-type channels serve pacemaking functions in both central neurons and cardiac nodal cells and support calcium signaling in secretory cells and vascular smooth muscle. They may also be involved in the modulation of firing patterns of neurons which is important for information processing as well as in cell growth processes.
Gene Name:
CACNA1H
Uniprot ID:
O95180
Molecular Weight:
259160.2 Da
References
  1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [1281221 ]
  2. Lewalter T, Pittrow D, Goette A, Kirch W, Hohnloser S: [Clinical pharmacology and electrophysiological properties of dronedarone]. Dtsch Med Wochenschr. 2010 Mar;135 Suppl 2:S43-7. doi: 10.1055/s-0030-1249208. Epub 2010 Mar 10. [20221978 ]
General Function:
Voltage-gated calcium channel activity
Specific Function:
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-type calcium channel (CACNA1A), N-type (CACNA1B), L-type (CACNA1C OR CACNA1D) and possibly T-type (CACNA1G). Overexpression induces apoptosis.
Gene Name:
CACNA2D2
Uniprot ID:
Q9NY47
Molecular Weight:
129816.095 Da
References
  1. Cohen CJ, Spires S, Van Skiver D: Block of T-type Ca channels in guinea pig atrial cells by antiarrhythmic agents and Ca channel antagonists. J Gen Physiol. 1992 Oct;100(4):703-28. [1281221 ]
  2. Lewalter T, Pittrow D, Goette A, Kirch W, Hohnloser S: [Clinical pharmacology and electrophysiological properties of dronedarone]. Dtsch Med Wochenschr. 2010 Mar;135 Suppl 2:S43-7. doi: 10.1055/s-0030-1249208. Epub 2010 Mar 10. [20221978 ]
General Function:
Receptor signaling protein activity
Specific Function:
Beta-adrenergic receptors mediate the catecholamine-induced activation of adenylate cyclase through the action of G proteins. This receptor binds epinephrine and norepinephrine with approximately equal affinity. Mediates Ras activation through G(s)-alpha- and cAMP-mediated signaling.
Gene Name:
ADRB1
Uniprot ID:
P08588
Molecular Weight:
51322.1 Da
References
  1. Doggrell SA, Brown L: Present and future pharmacotherapy for heart failure. Expert Opin Pharmacother. 2002 Jul;3(7):915-30. [12083991 ]