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Record Information
Version5.0
StatusExpected but not Quantified
Creation Date2012-09-06 15:16:51 UTC
Update Date2021-09-14 15:00:47 UTC
HMDB IDHMDB0015058
Secondary Accession Numbers
  • HMDB15058
Metabolite Identification
Common NameLevosimendan
DescriptionLevosimendan, also known as simdax, belongs to the class of organic compounds known as phenylhydrazines. Phenylhydrazines are compounds containing a phenylhydrazide moiety, which consists of a hydrazide substituent attached to a phenyl group. Levosimendan is marketed as a 2.5 mg/mL concentrated solution for IV infusion. Levosimendan is a drug which is used for short term treatment of acutely decompensated severe chronic heart failure (chf). also being investigated for use/treatment in heart disease. Levosimendan is a strong basic compound (based on its pKa). It also has a vasodilatory effect, by opening adenosine triphosphate (ATP)-sensitive potassium channels in vascular smooth muscle to cause smooth muscle relaxation. However, the drug was proven to be superior to dobutamine for treating patients with a history of CHF or those on beta-blocker therapy when they are hospitalized with acute decompensations.The Orion Corporation originally developed levosimendan and applied for a new drug application in 1998 in the U.S. In total, the clinical data base includes more than 3500 patients in Phase IIb and III double-blind randomized studies. Levosimendan (INN) is a calcium sensitiser used in the management of acutely decompensated congestive heart failure. Initially, Orion obtained the approval to market the drug in Sweden in 2000. It is marketed under the trade name Simdax (Orion Corporation). Common adverse drug reactions (≥1% of patients) associated with levosimendan therapy include: headache, hypotension, arrhythmias (atrial fibrillation, extrasystoles, Atrial tachycardia, ventricular tachycardia), myocardial ischaemia, hypokalaemia and/or nausea (Rossi, 2006).
Structure
Data?1582753252
Synonyms
ValueSource
LevosimendanumChEBI
SimdaxChEBI
LevosimedanHMDB
SimadaxHMDB
DextrosimendanHMDB
((4-(1,4,5,6-Tetrahydro-4-methyl-6-oxo-3-pyridazinyl)phenyl)hydrazono)propanedinitrileHMDB
SimendanHMDB
Chemical FormulaC14H12N6O
Average Molecular Weight280.2847
Monoisotopic Molecular Weight280.107259036
IUPAC Name1-cyano-N-{4-[(4R)-4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl]phenyl}methanecarbohydrazonoyl cyanide
Traditional Namelevosimendan
CAS Registry Number141505-33-1
SMILES
C[C@@H]1CC(=O)NN=C1C1=CC=C(NN=C(C#N)C#N)C=C1
InChI Identifier
InChI=1S/C14H12N6O/c1-9-6-13(21)19-20-14(9)10-2-4-11(5-3-10)17-18-12(7-15)8-16/h2-5,9,17H,6H2,1H3,(H,19,21)/t9-/m1/s1
InChI KeyWHXMKTBCFHIYNQ-SECBINFHSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as phenylhydrazines. Phenylhydrazines are compounds containing a phenylhydrazide moiety, which consists of a hydrazide substituent attached to a phenyl group.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassPhenylhydrazines
Direct ParentPhenylhydrazines
Alternative Parents
Substituents
  • Phenylhydrazine
  • Pyridazinone
  • Pyridazine
  • Carboxylic acid derivative
  • Hydrazone
  • Carbonitrile
  • Nitrile
  • Organoheterocyclic compound
  • Azacycle
  • Organic nitrogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Organopnictogen compound
  • Carbonyl group
  • Hydrocarbon derivative
  • Organic oxide
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Ontology
Disposition

Biological location

Source

Route of exposure

Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility0.088 g/LNot Available
LogPNot AvailableNot Available
Experimental Spectral PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
Water Solubility0.088 g/LALOGPS
logP10(2.69) g/LALOGPS
logP10(2.16) g/LChemAxon
logS10(-3.5) g/LALOGPS
pKa (Strongest Acidic)10.53ChemAxon
pKa (Strongest Basic)4.91ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area113.43 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity77.63 m³·mol⁻¹ChemAxon
Polarizability28.67 ųChemAxon
Number of Rings2ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Spectral Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DarkChem[M+H]+166.91131661259
DarkChem[M-H]-167.67831661259

Predicted Kovats Retention Indices

Not Available
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Levosimendan GC-MS (Non-derivatized) - 70eV, Positivesplash10-0l6r-2190000000-95c9a8cdabf61909acac2017-09-01Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Levosimendan GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Experimental LC-MS/MSLC-MS/MS Spectrum - Levosimendan LC-ESI-qTof , Positive-QTOFsplash10-001i-0390000000-88e46fb95115eb7b2d262017-09-14HMDB team, MONAView Spectrum
Experimental LC-MS/MSLC-MS/MS Spectrum - Levosimendan , positive-QTOFsplash10-001i-0390000000-88e46fb95115eb7b2d262017-09-14HMDB team, MONAView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Levosimendan 10V, Positive-QTOFsplash10-01q9-1290000000-6d9a7b470636a54e587e2016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Levosimendan 20V, Positive-QTOFsplash10-0gx0-1390000000-90a2f0832ca10328f83c2016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Levosimendan 40V, Positive-QTOFsplash10-000f-9620000000-c8bae586e1e611afe4c62016-08-01Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Levosimendan 10V, Negative-QTOFsplash10-004i-4090000000-267416d8b7d793ecaf282016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Levosimendan 20V, Negative-QTOFsplash10-0006-9150000000-f151e544be5e67b5ad212016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Levosimendan 40V, Negative-QTOFsplash10-004l-9010000000-532ba1389514437da33a2016-08-03Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Levosimendan 10V, Positive-QTOFsplash10-001i-0090000000-5a694436ae56bc0fded42021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Levosimendan 20V, Positive-QTOFsplash10-001i-0190000000-47192e7bd78a3e6e189b2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Levosimendan 40V, Positive-QTOFsplash10-000i-1930000000-5a28d318150afb2c5a9c2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Levosimendan 10V, Negative-QTOFsplash10-004i-0090000000-d2087bfe0706f27ab2732021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Levosimendan 20V, Negative-QTOFsplash10-004i-2090000000-6f5783406fb63b34609e2021-10-11Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Levosimendan 40V, Negative-QTOFsplash10-0aor-5490000000-cd828b665b63c98858cb2021-10-11Wishart LabView Spectrum
Biological Properties
Cellular Locations
  • Membrane
Biospecimen Locations
  • Blood
  • Urine
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00922 details
UrineExpected but not QuantifiedNot QuantifiedNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00922 details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00922
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID2298414
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkLevosimendan
METLIN IDNot Available
PubChem Compound3033825
PDB IDNot Available
ChEBI ID50567
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Kasikcioglu HA, Cam N: A review of levosimendan in the treatment of heart failure. Vasc Health Risk Manag. 2006;2(4):389-400. [PubMed:17323593 ]
  2. Mebazaa A, Nieminen MS, Packer M, Cohen-Solal A, Kleber FX, Pocock SJ, Thakkar R, Padley RJ, Poder P, Kivikko M: Levosimendan vs dobutamine for patients with acute decompensated heart failure: the SURVIVE Randomized Trial. JAMA. 2007 May 2;297(17):1883-91. [PubMed:17473298 ]
  3. MedicinesComplete [Link]

Enzymes

General function:
Involved in catalytic activity
Specific function:
Cyclic nucleotide phosphodiesterase with a dual-specificity for the second messengers cAMP and cGMP, which are key regulators of many important physiological processes (By similarity).
Gene Name:
PDE3A
Uniprot ID:
Q14432
Molecular weight:
124978.06
References
  1. Szilagyi S, Pollesello P, Levijoki J, Haikala H, Bak I, Tosaki A, Borbely A, Edes I, Papp Z: Two inotropes with different mechanisms of action: contractile, PDE-inhibitory and direct myofibrillar effects of levosimendan and enoximone. J Cardiovasc Pharmacol. 2005 Sep;46(3):369-76. [PubMed:16116344 ]
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. Yildiz O: Vasodilating mechanisms of levosimendan: involvement of K+ channels. J Pharmacol Sci. 2007 May;104(1):1-5. Epub 2007 Apr 24. [PubMed:17452812 ]
General function:
Involved in calcium ion binding
Specific function:
Troponin is the central regulatory protein of striated muscle contraction. Tn consists of three components:Tn-I which is the inhibitor of actomyosin ATPase, Tn-T which contains the binding site for tropomyosin and Tn-C. The binding of calcium to Tn-C abolishes the inhibitory action of Tn on actin filaments
Gene Name:
TNNC1
Uniprot ID:
P63316
Molecular weight:
18402.4
References
  1. Kleerekoper Q, Putkey JA: Drug binding to cardiac troponin C. J Biol Chem. 1999 Aug 20;274(34):23932-9. [PubMed:10446160 ]
  2. Levijoki J, Pollesello P, Kaivola J, Tilgmann C, Sorsa T, Annila A, Kilpelainen I, Haikala H: Further evidence for the cardiac troponin C mediated calcium sensitization by levosimendan: structure-response and binding analysis with analogs of levosimendan. J Mol Cell Cardiol. 2000 Mar;32(3):479-91. [PubMed:10731446 ]
  3. Sorsa T, Heikkinen S, Abbott MB, Abusamhadneh E, Laakso T, Tilgmann C, Serimaa R, Annila A, Rosevear PR, Drakenberg T, Pollesello P, Kilpelainen I: Binding of levosimendan, a calcium sensitizer, to cardiac troponin C. J Biol Chem. 2001 Mar 23;276(12):9337-43. Epub 2000 Dec 11. [PubMed:11113122 ]
  4. Sorsa T, Pollesello P, Permi P, Drakenberg T, Kilpelainen I: Interaction of levosimendan with cardiac troponin C in the presence of cardiac troponin I peptides. J Mol Cell Cardiol. 2003 Sep;35(9):1055-61. [PubMed:12967628 ]
  5. Lehmann A, Boldt J, Lang J, Isgro F, Blome M: [Is levosimendan an inoprotective drug in patients with acute coronary syndrome undergoing surgical revascularization?]. Anasthesiol Intensivmed Notfallmed Schmerzther. 2003 Sep;38(9):577-82. [PubMed:12975736 ]
  6. 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 inward rectifier potassium channel activity
Specific function:
This potassium channel 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 external barium
Gene Name:
KCNJ8
Uniprot ID:
Q15842
Molecular weight:
47967.5
References
  1. Yildiz O: Vasodilating mechanisms of levosimendan: involvement of K+ channels. J Pharmacol Sci. 2007 May;104(1):1-5. Epub 2007 Apr 24. [PubMed:17452812 ]