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Record Information
Version4.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:49 UTC
Update Date2017-10-23 19:06:17 UTC
HMDB IDHMDB0014453
Secondary Accession Numbers
  • HMDB14453
Metabolite Identification
Common NameIbutilide
DescriptionIbutilide is only found in individuals that have used or taken this drug. It is a Class III antiarrhythmic agent that is indicated for acute cardioconversion of atrial fibrillation and atrial flutter of a recent onset to sinus rhythm. [Wikipedia]Ibutilide is a 'pure' class III antiarrhythmic drug, used intravenously against atrial flutter and fibrillation. At a cellular level it exerts two main actions: induction of a persistent Na+ current sensitive to dihydropyridine Ca2+ channel blockers and potent inhibition of the cardiac rapid delayed rectifier K+ current, by binding within potassium channel pores. In other words, Ibutilide binds to and alters the activity of hERG potassium channels, delayed inward rectifier potassium (IKr) channels and L-type (dihydropyridine sensitive) calcium channels
Structure
Thumb
Synonyms
ValueSource
Ibutilide fumarateHMDB
Ibutilide, (+)-isomerMeSH
N-(4-(4-(ethylheptylamino)-1-Hydroxybutyl)phenyl)methanesulfonamideMeSH
Ibutilide, (+-)-isomerMeSH
Ibutilide, fumarate salt (2:1), (+-)-isomerMeSH
CorvertMeSH
Ibutilide, (-)-isomerMeSH
Ibutilide, fumarate salt (2:1), (+)-isomerMeSH
Chemical FormulaC20H36N2O3S
Average Molecular Weight384.576
Monoisotopic Molecular Weight384.244663718
IUPAC NameN-(4-{4-[ethyl(heptyl)amino]-1-hydroxybutyl}phenyl)methanesulfonamide
Traditional Nameibutilide
CAS Registry Number122647-32-9
SMILES
CCCCCCCN(CC)CCCC(O)C1=CC=C(NS(C)(=O)=O)C=C1
InChI Identifier
InChI=1S/C20H36N2O3S/c1-4-6-7-8-9-16-22(5-2)17-10-11-20(23)18-12-14-19(15-13-18)21-26(3,24)25/h12-15,20-21,23H,4-11,16-17H2,1-3H3
InChI KeyALOBUEHUHMBRLE-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of chemical entities known as phenylbutylamines. These are compounds containing a phenylbutylamine moiety, which consists of a phenyl group substituted at the fourth carbon by an butan-1-amine.
KingdomChemical entities
Super ClassOrganic compounds
ClassBenzenoids
Sub ClassBenzene and substituted derivatives
Direct ParentPhenylbutylamines
Alternative Parents
Substituents
  • Phenylbutylamine
  • Sulfanilide
  • Aralkylamine
  • Organic sulfonic acid amide
  • Organosulfonic acid amide
  • Organic sulfonic acid or derivatives
  • Organosulfonic acid or derivatives
  • Aminosulfonyl compound
  • Sulfonyl
  • Secondary alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Alcohol
  • Hydrocarbon derivative
  • Organic oxide
  • Organic oxygen compound
  • Organopnictogen compound
  • Organic nitrogen compound
  • Organosulfur compound
  • Organooxygen compound
  • Organonitrogen compound
  • Aromatic alcohol
  • Amine
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
Disposition

Biological Location:

  Subcellular:

  Biofluid and excreta:

Process

Naturally occurring process:

  Biological process:

    Biochemical pathway:

Role

Industrial application:

  Pharmaceutical industry:

    Cardiovascular drug:

Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.0047 g/LNot Available
LogP4.6Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0047 g/LALOGPS
logP4.72ALOGPS
logP2.54ChemAxon
logS-4.9ALOGPS
pKa (Strongest Acidic)9.72ChemAxon
pKa (Strongest Basic)10.4ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area69.64 ŲChemAxon
Rotatable Bond Count13ChemAxon
Refractivity109.18 m³·mol⁻¹ChemAxon
Polarizability46.45 ųChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0udi-3494000000-4216adb870d24524f3f8View in MoNA
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (1 TMS) - 70eV, Positivesplash10-00di-7594700000-e10d1f60942f779d0b69View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00kr-1049000000-878a4988359cc2b11375View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00du-1291000000-8799afa11da8453ab702View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0595-9440000000-b36c8a40d5b1b8695387View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-003r-6009000000-c0b15b1b2eb0e206020fView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-004i-9002000000-a45fd07019d442a5c6b5View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-004i-9000000000-5d0b14017a866bd34adaView in MoNA
Biological Properties
Cellular Locations
  • Cytoplasm
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
Pathways
NameSMPDB/PathwhizKEGG
Ibutilide PathwayPw000385Pw000385 greyscalePw000385 simpleNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00308 details
UrineExpected but not Quantified Not AvailableNot AvailableTaking drug identified by DrugBank entry DB00308 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00308
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID54755
KEGG Compound IDC07753
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkIbutilide
METLIN IDNot Available
PubChem Compound60753
PDB IDNot Available
ChEBI ID112608
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General ReferencesNot Available

Enzymes

General function:
Involved in ion channel activity
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). Isoform 3 has no channel activity by itself, but modulates channel characteristics when associated with isoform 1
Gene Name:
KCNH2
Uniprot ID:
Q12809
Molecular weight:
126653.5
References
  1. Perry M, de Groot MJ, Helliwell R, Leishman D, Tristani-Firouzi M, Sanguinetti MC, Mitcheson J: Structural determinants of HERG channel block by clofilium and ibutilide. Mol Pharmacol. 2004 Aug;66(2):240-9. [PubMed:15266014 ]
  2. Perry M, Stansfeld PJ, Leaney J, Wood C, de Groot MJ, Leishman D, Sutcliffe MJ, Mitcheson JS: Drug binding interactions in the inner cavity of HERG channels: molecular insights from structure-activity relationships of clofilium and ibutilide analogs. Mol Pharmacol. 2006 Feb;69(2):509-19. Epub 2005 Nov 16. [PubMed:16291873 ]
  3. Wolpert C, Schimpf R, Veltmann C, Borggrefe M: [Short QT syndrome]. Herz. 2007 May;32(3):206-10. [PubMed:17497253 ]
  4. Wolpert C, Schimpf R, Veltmann C, Giustetto C, Gaita F, Borggrefe M: Clinical characteristics and treatment of short QT syndrome. Expert Rev Cardiovasc Ther. 2005 Jul;3(4):611-7. [PubMed:16076272 ]
  5. Yang T, Snyders D, Roden DM: Drug block of I(kr): model systems and relevance to human arrhythmias. J Cardiovasc Pharmacol. 2001 Nov;38(5):737-44. [PubMed:11602820 ]
  6. Doggrell SA, Hancox JC: Ibutilide--recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. [PubMed:15926871 ]
General function:
Involved in ion channel activity
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-1C gives rise to L-type calcium currents. Long-lasting (L-type) calcium channels belong to the 'high-voltage activated' (HVA) group. They are blocked by dihydropyridines (DHP), phenylalkylamines, benzothiazepines, and by omega-agatoxin-IIIA (omega-Aga-IIIA). They are however insensitive to omega-conotoxin- GVIA (omega-CTx-GVIA) and omega-agatoxin-IVA (omega-Aga-IVA). Calcium channels containing the alpha-1C subunit play an important role in excitation-contraction coupling in the heart. The various isoforms display marked differences in the sensitivity to DHP compounds. Binding of calmodulin or CABP1 at the same regulatory sites results in an opposit effects on the channel function
Gene Name:
CACNA1C
Uniprot ID:
Q13936
Molecular weight:
248974.1
References
  1. Doggrell SA, Hancox JC: Ibutilide--recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. [PubMed:15926871 ]
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. [PubMed:9257085 ]
  3. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]
General function:
Involved in ion channel activity
Specific function:
Pore-forming (alpha) subunit of voltage-gated potassium channel. Elicits a slowly activating, rectifying current. Channel properties may be modulated by cAMP and subunit assembly
Gene Name:
KCNH6
Uniprot ID:
Q9H252
Molecular weight:
109923.7
References
  1. Doggrell SA, Hancox JC: Ibutilide--recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. [PubMed:15926871 ]
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. [PubMed:9257085 ]
General function:
Involved in inward rectifier potassium channel activity
Specific function:
This receptor is controlled by G proteins. Inward rectifier potassium channels are characterized by a greater tendency to allow potassium to flow into the cell rather than out of it. Their voltage dependence is regulated by the concentration of extracellular potassium; as external potassium is raised, the voltage range of the channel opening shifts to more positive voltages. The inward rectification is mainly due to the blockage of outward current by internal magnesium. Can be blocked by extracellular barium
Gene Name:
KCNJ11
Uniprot ID:
Q14654
Molecular weight:
43540.4
References
  1. Doggrell SA, Hancox JC: Ibutilide--recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. [PubMed:15926871 ]
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. [PubMed:9257085 ]
General function:
Involved in metal ion binding
Specific function:
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Plays an important role in excitation-contraction coupling
Gene Name:
CACNA2D1
Uniprot ID:
P54289
Molecular weight:
124566.9
References
  1. Doggrell SA, Hancox JC: Ibutilide--recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. [PubMed:15926871 ]
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. [PubMed:9257085 ]
General function:
Involved in voltage-gated calcium channel activity
Specific function:
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and inactivation, modulating G protein inhibition and controlling the alpha-1 subunit membrane targeting
Gene Name:
CACNB1
Uniprot ID:
Q02641
Molecular weight:
65713.0
References
  1. Doggrell SA, Hancox JC: Ibutilide--recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. [PubMed:15926871 ]
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. [PubMed:9257085 ]
General function:
Involved in voltage-gated calcium channel activity
Specific function:
This protein is a subunit of the dihydropyridine (DHP) sensitive calcium channel. Plays a role in excitation-contraction coupling. The skeletal muscle DHP-sensitive Ca(2+) channel may function only as a multiple subunit complex
Gene Name:
CACNG1
Uniprot ID:
Q06432
Molecular weight:
25028.1
References
  1. Doggrell SA, Hancox JC: Ibutilide--recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. [PubMed:15926871 ]
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. [PubMed:9257085 ]
General function:
Involved in ion channel activity
Specific function:
Pore-forming (alpha) subunit of voltage-gated potassium channel. Channel properties may be modulated by cAMP and subunit assembly
Gene Name:
KCNH7
Uniprot ID:
Q9NS40
Molecular weight:
134998.5
References
  1. Doggrell SA, Hancox JC: Ibutilide--recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. [PubMed:15926871 ]
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. [PubMed:9257085 ]
General function:
Involved in potassium channel activity
Specific function:
Weakly inward rectifying potassium channel
Gene Name:
KCNK1
Uniprot ID:
O00180
Molecular weight:
38142.8
References
  1. Doggrell SA, Hancox JC: Ibutilide--recent molecular insights and accumulating evidence for use in atrial flutter and fibrillation. Expert Opin Investig Drugs. 2005 May;14(5):655-69. [PubMed:15926871 ]
  2. Foster RH, Wilde MI, Markham A: Ibutilide. A review of its pharmacological properties and clinical potential in the acute management of atrial flutter and fibrillation. Drugs. 1997 Aug;54(2):312-30. [PubMed:9257085 ]