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Record Information
Version3.6
Creation Date2012-09-06 15:16:49 UTC
Update Date2016-02-11 01:28:39 UTC
HMDB IDHMDB14468
Secondary Accession NumbersNone
Metabolite Identification
Common NameTolcapone
DescriptionTolcapone is a drug that inhibits the enzyme catechol-O-methyl transferase (COMT). It is used in the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa medication. It is a yellow, odorless, non-hygroscopic, crystalline compound. Tolcapone is associated with a risk of hepatotoxicity. [Wikipedia]
Structure
Thumb
Synonyms
ValueSource
3,4-Dihydroxy-4'-methyl-5-nitrobenzophenoneChEBI
3,4-Dihydroxy-5-nitro-4'-methylbenzophenoneChEBI
4'-Methyl-3,4-dihydroxy-5-nitrobenzophenoneChEBI
Chemical FormulaC14H11NO5
Average Molecular Weight273.2408
Monoisotopic Molecular Weight273.063722467
IUPAC Name5-(4-methylbenzoyl)-3-nitrobenzene-1,2-diol
Traditional Nametolcapone
CAS Registry Number134308-13-7
SMILES
CC1=CC=C(C=C1)C(=O)C1=CC(=C(O)C(O)=C1)[N+]([O-])=O
InChI Identifier
InChI=1S/C14H11NO5/c1-8-2-4-9(5-3-8)13(17)10-6-11(15(19)20)14(18)12(16)7-10/h2-7,16,18H,1H3
InChI KeyInChIKey=MIQPIUSUKVNLNT-UHFFFAOYSA-N
Chemical Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzophenones. These are organic compounds containing a ketone attached to two phenyl groups.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzophenones
Direct ParentBenzophenones
Alternative Parents
Substituents
  • Benzophenone
  • Diphenylmethane
  • Nitrophenol derivative
  • Nitrobenzene
  • Acetophenone
  • Aryl ketone
  • 1,2-diphenol
  • Benzoyl
  • Toluene
  • Phenol
  • Organic nitro compound
  • Organic nitrite
  • C-nitro compound
  • Ketone
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic oxoazanium
  • Hydrocarbon derivative
  • Organic salt
  • Organooxygen compound
  • Organonitrogen compound
  • Organic zwitterion
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Ontology
StatusExpected but not Quantified
Origin
  • Drug
Biofunction
  • Antidyskinetics
  • Antiparkinson Agents
  • Central Nervous System Agents
  • Enzyme Inhibitors
Application
  • Pharmaceutical
Cellular locations
  • Extracellular
  • Membrane
Physical Properties
StateSolid
Experimental Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water Solubility5.69e-02 g/LNot Available
LogP4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.057 mg/mLALOGPS
logP2.63ALOGPS
logP3.28ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)5.17ChemAxon
pKa (Strongest Basic)-6.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area103.35 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity72.96 m3·mol-1ChemAxon
Polarizability26.44 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
Biological Properties
Cellular Locations
  • Extracellular
  • Membrane
Biofluid Locations
  • Blood
  • Urine
Tissue LocationNot Available
PathwaysNot Available
Normal Concentrations
BiofluidStatusValueAgeSexConditionReferenceDetails
BloodExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00323
  • Not Applicable
details
UrineExpected but not QuantifiedNot ApplicableNot AvailableNot AvailableTaking drug identified by DrugBank entry DB00323
  • Not Applicable
details
Abnormal Concentrations
Not Available
Predicted Concentrations
BiofluidValueOriginal ageOriginal sexOriginal conditionComments
Blood0-4 uMAdult (>18 years old)BothNormalPredicted based on drug qualities
Blood0-2 umol/mmol creatinineAdult (>18 years old)BothNormalPredicted based on drug qualities
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB00323
DrugBank Metabolite IDNot Available
Phenol Explorer Compound IDNot Available
Phenol Explorer Metabolite IDNot Available
FoodDB IDNot Available
KNApSAcK IDNot Available
Chemspider ID3848682
KEGG Compound IDC07949
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkTolcapone
NuGOwiki LinkHMDB14468
Metagene LinkHMDB14468
METLIN IDNot Available
PubChem Compound4659569
PDB IDTCW
ChEBI ID63630
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Guay DR: Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of Parkinson's disease. Pharmacotherapy. 1999 Jan;19(1):6-20. [9917075 ]
  2. Keating GM, Lyseng-Williamson KA: Tolcapone: a review of its use in the management of Parkinson's disease. CNS Drugs. 2005;19(2):165-84. [15697329 ]
  3. Truong DD: Tolcapone: review of its pharmacology and use as adjunctive therapy in patients with Parkinson's disease. Clin Interv Aging. 2009;4:109-13. Epub 2009 May 14. [19503773 ]
  4. Forsberg M, Lehtonen M, Heikkinen M, Savolainen J, Jarvinen T, Mannisto PT: Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat. J Pharmacol Exp Ther. 2003 Feb;304(2):498-506. [12538800 ]
  5. Kaakkola S: Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. Drugs. 2000 Jun;59(6):1233-50. [10882160 ]

Enzymes

General function:
Involved in magnesium ion binding
Specific function:
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
Gene Name:
COMT
Uniprot ID:
P21964
Molecular weight:
30036.77
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. Ries V, Selzer R, Eichhorn T, Oertel WH, Eggert K: Replacing a dopamine agonist by the COMT-inhibitor tolcapone as an adjunct to L-dopa in the treatment of Parkinson's disease: a randomized, multicenter, open-label, parallel-group study. Clin Neuropharmacol. 2010 May;33(3):142-50. [20502133 ]
  3. Guay DR: Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of Parkinson's disease. Pharmacotherapy. 1999 Jan;19(1):6-20. [9917075 ]
  4. Keating GM, Lyseng-Williamson KA: Tolcapone: a review of its use in the management of Parkinson's disease. CNS Drugs. 2005;19(2):165-84. [15697329 ]
  5. Truong DD: Tolcapone: review of its pharmacology and use as adjunctive therapy in patients with Parkinson's disease. Clin Interv Aging. 2009;4:109-13. Epub 2009 May 14. [19503773 ]
  6. Apud JA, Mattay V, Chen J, Kolachana BS, Callicott JH, Rasetti R, Alce G, Iudicello JE, Akbar N, Egan MF, Goldberg TE, Weinberger DR: Tolcapone improves cognition and cortical information processing in normal human subjects. Neuropsychopharmacology. 2007 May;32(5):1011-20. Epub 2006 Oct 25. [17063156 ]
  7. Stocchi F, De Pandis MF: Utility of tolcapone in fluctuating Parkinson's disease. Clin Interv Aging. 2006;1(4):317-25. [18046910 ]
  8. Forsberg M, Lehtonen M, Heikkinen M, Savolainen J, Jarvinen T, Mannisto PT: Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat. J Pharmacol Exp Ther. 2003 Feb;304(2):498-506. [12538800 ]
  9. Tai CH, Wu RM: Catechol-O-methyltransferase and Parkinson's disease. Acta Med Okayama. 2002 Feb;56(1):1-6. [11873938 ]
  10. Kaakkola S: Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. Drugs. 2000 Jun;59(6):1233-50. [10882160 ]
  11. Ruottinen HM, Rinne UK: COMT inhibition in the treatment of Parkinson's disease. J Neurol. 1998 Nov;245(11 Suppl 3):P25-34. [9808337 ]
General function:
Involved in monooxygenase activity
Specific function:
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:
CYP2C9
Uniprot ID:
P11712
Molecular weight:
55627.365
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. [19934256 ]