Tolcapone (T3D2751)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (1)XML
Targets (1)
Record Information
Version2.0
Creation Date2009-07-21 20:26:36 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2751
Identification
Common NameTolcapone
ClassSmall Molecule
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.
Compound Type
  • Antidyskinetic
  • Antiparkinson Agent
  • Central Nervous System Agent
  • Drug
  • Enzyme Inhibitor
  • Ester
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
Synonym
(3,4-dihydroxy-5-nitrophenyl)(4-methylphenyl)methanone
3,4-Dihydroxy-4'-methyl-5-nitrobenzophenone
3,4-Dihydroxy-5-nitro-4'-methylbenzophenone
4'-Methyl-3,4-dihydroxy-5-nitrobenzophenone
Sen De Ning
Tasmar
Tolcapon
Tolcapona
Tolcaponum
Chemical FormulaC14H11NO5
Average Molecular Mass273.241 g/mol
Monoisotopic Mass273.064 g/mol
CAS Registry Number134308-13-7
IUPAC Name5-(4-methylbenzoyl)-3-nitrobenzene-1,2-diol
Traditional Nametolcapone
SMILESCC1=CC=C(C=C1)C(=O)C1=CC(=C(O)C(O)=C1)N(=O)=O
InChI IdentifierInChI=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
Description 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
  • Aryl-phenylketone
  • Nitrophenol
  • Nitrobenzene
  • Nitroaromatic compound
  • Benzoyl
  • Catechol
  • Aryl ketone
  • 1-hydroxy-4-unsubstituted benzenoid
  • 1-hydroxy-2-unsubstituted benzenoid
  • Toluene
  • Phenol
  • Ketone
  • Organic nitro compound
  • C-nitro compound
  • Organic 1,3-dipolar compound
  • Propargyl-type 1,3-dipolar organic compound
  • Allyl-type 1,3-dipolar organic compound
  • Organic oxoazanium
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Organic oxide
  • Organic oxygen compound
  • Organopnictogen compound
  • Organonitrogen compound
  • Organooxygen compound
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Extracellular
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical Roles
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility5.69e-02 g/L
LogP4
Predicted Properties
PropertyValueSource
Water Solubility0.057 g/LALOGPS
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 ŲChemAxon
Rotatable Bond Count3ChemAxon
Refractivity72.96 m³·mol⁻¹ChemAxon
Polarizability26.44 ųChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0q29-3970000000-6534afd6ea55a8b8f9232017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00xr-9748400000-548249e165d1b79700042017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00e9-0980000000-495401c19ad2c2091c1a2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00e9-0980000000-495401c19ad2c2091c1a2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-001i-0940000000-7e03275a1aab614db33e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-0159-0900000000-58b8b095bc956f6633202021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-00lr-0910000000-97d2e08975916b96961d2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-0159-0900000000-64283697ac79a1be77ba2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-001i-0940000000-d7c768583cd479e96f712021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-05c6-0390000000-f450d9a92858b34035482021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-00di-0090000000-d84e09a33f805ed7a7002021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-00lr-0910000000-20fd9f346adeaefc64952021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-00di-0090000000-2f9b35f27dfa158fbe472021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0090000000-88737fd9fe3cbdd7038b2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-0090000000-4b7de2c2d046ee8b3b1e2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0hb9-1970000000-b9055dada9fa16c1703e2016-08-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0090000000-7963016dae7c1913c6152016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0090000000-17f517c83922302980432016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00di-5190000000-9b0a168ebf7e529ad1f22016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0390000000-be3569c1ee47e9ff087f2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00xr-4890000000-d2acd7d77e0195bb275b2021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00mo-9510000000-81222ad94f6a6eb453192021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0090000000-41d62228dd74750350152021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0090000000-02a4ae01ccd77f2e84e82021-09-22View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0007-8900000000-4c7370b8810f64b3021d2021-09-22View Spectrum
Toxicity Profile
Route of ExposureOral, rapidly absorbed (absolute bioavailability is about 65%)
Mechanism of ToxicityTolcapone hepatoxicity can be attributed to elevated levels of transminases, but studies have shown that minimal risk exists for those without preexisting liver conditions when their enzyme levels were being monitored. No clear mechanism is implicated in tolcapone induced liver toxicity, but it has been hypothesized that it has something to do with abnormal mitochondrial respiration due to the uncoupling of oxidative phosphorylation. Dyskinesia occurs because the administration of Tolcapone results in the accumulation of the biological methyl donor S-adenosyl-L-methionine (SAM) in the striatum that works to induce symptoms of Parkinson's disease. (Wikipedia)
MetabolismThe main metabolic pathway of tolcapone is glucuronidation. Route of Elimination: Tolcapone is almost completely metabolized prior to excretion, with only a very small amount (0.5% of dose) found unchanged in urine. The glucuronide conjugate of tolcapone is mainly excreted in the urine but is also excreted in the bile. Half Life: 2-3.5 hours
Toxicity ValuesLD50: 1600 mg/kg (Oral, Rats) (1)
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesUsed as an adjunct to levodopa/carbidopa therapy for the symptomatic treatment of Parkinson's Disease. This drug is generally reserved for patients with parkinsonian syndrome receiving levodopa/carbidopa who are experiencing symptom fluctuations and are not responding adequately to or are not candidates for other adjunctive therapies.
Minimum Risk LevelNot Available
Health EffectsTolcapone has demonstrated significant hepatotoxicity that limits the drug's utility. Other side effects that result from the administration of Tolcapone regard the increase in dopaminergic activity, digestive symptoms and liver function. Treatment with tolcapone runs the risk of eliciting or prolonging dyskinesia. (Wikipedia)
SymptomsDigestive symptoms include nausea, diarrhea, orthostatic hypotension, urine discoloration and dizziness. Tolcapone causes more severe diarrhea than entacapone. (Wikipedia)
TreatmentHospitalization is advised. General supportive care is indicated. (8) Tolcapone-induced dyskinesia can be counteracted by decreasing the dose of L-DOPA (Wikipedia).
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00323
HMDB IDHMDB14468
PubChem Compound ID4659569
ChEMBL IDCHEMBL1324
ChemSpider ID3848682
KEGG IDC07949
UniProt IDNot Available
OMIM ID
ChEBI ID63630
BioCyc IDCPD-7664
CTD IDNot Available
Stitch IDTolcapone
PDB IDTCW
ACToR IDNot Available
Wikipedia LinkTolcapone
References
Synthesis ReferenceNot Available
MSDSLink
General References
  1. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  2. Guay DR: Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of Parkinson's disease. Pharmacotherapy. 1999 Jan;19(1):6-20. [9917075 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. Kaakkola S: Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. Drugs. 2000 Jun;59(6):1233-50. [10882160 ]
  7. Drugs.com [Link]
  8. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Catechol O-methyltransferase
General Function:
O-methyltransferase activity
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 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]