Tolcapone (CHEM002170)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (1)XML
Record Information
Version1.0
Creation Date2009-07-21 20:26:36 UTC
Update Date2026-03-27 01:33:11 UTC
Accession NumberCHEM002170
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.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Antidyskinetic
  • Antiparkinson Agent
  • Central Nervous System Agent
  • Drug
  • Enzyme Inhibitor
  • Ester
  • Metabolite
  • Organic Compound
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
3,4-Dihydroxy-4'-methyl-5-nitrobenzophenoneChEBI
3,4-Dihydroxy-5-nitro-4'-methylbenzophenoneChEBI
4'-Methyl-3,4-dihydroxy-5-nitrobenzophenoneChEBI
TasmarKegg
Roche brand OF tolcaponeHMDB
3,4-Dihydroxy-5'-methyl-5-nitrobenzophenoneHMDB
3,4 Dihydroxy 5' methyl 5 nitrobenzophenoneHMDB
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 KeyMIQPIUSUKVNLNT-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
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 RuleNoChemAxon
MDDR-like RuleNoChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0q29-3970000000-6534afd6ea55a8b8f923Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (2 TMS) - 70eV, Positivesplash10-00xr-9748400000-548249e165d1b7970004Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-00e9-0980000000-495401c19ad2c2091c1aSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00e9-0980000000-495401c19ad2c2091c1aSpectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Positivesplash10-001i-0940000000-7e03275a1aab614db33eSpectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Negativesplash10-0159-0900000000-58b8b095bc956f663320Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Negativesplash10-00lr-0910000000-97d2e08975916b96961dSpectrum
LC-MS/MSLC-MS/MS Spectrum - 90V, Positivesplash10-0159-0900000000-64283697ac79a1be77baSpectrum
LC-MS/MSLC-MS/MS Spectrum - 60V, Negativesplash10-001i-0940000000-d7c768583cd479e96f71Spectrum
LC-MS/MSLC-MS/MS Spectrum - 45V, Negativesplash10-05c6-0390000000-f450d9a92858b3403548Spectrum
LC-MS/MSLC-MS/MS Spectrum - 15V, Negativesplash10-00di-0090000000-d84e09a33f805ed7a700Spectrum
LC-MS/MSLC-MS/MS Spectrum - 75V, Positivesplash10-00lr-0910000000-20fd9f346adeaefc6495Spectrum
LC-MS/MSLC-MS/MS Spectrum - 30V, Negativesplash10-00di-0090000000-2f9b35f27dfa158fbe47Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0090000000-88737fd9fe3cbdd7038bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00di-0090000000-4b7de2c2d046ee8b3b1eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0hb9-1970000000-b9055dada9fa16c1703eSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0090000000-7963016dae7c1913c615Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0090000000-17f517c8392230298043Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00di-5190000000-9b0a168ebf7e529ad1f2Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0390000000-be3569c1ee47e9ff087fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00xr-4890000000-d2acd7d77e0195bb275bSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00mo-9510000000-81222ad94f6a6eb45319Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-00di-0090000000-41d62228dd7475035015Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-00di-0090000000-02a4ae01ccd77f2e84e8Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0007-8900000000-4c7370b8810f64b3021dSpectrum
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).
Concentrations
Not Available
DrugBank IDDB00323
HMDB IDHMDB0014468
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDTCW
Wikipedia LinkTolcapone
Chemspider ID3848682
ChEBI ID63630
PubChem Compound ID4659569
Kegg Compound IDC07949
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis ReferenceNot Available
MSDSLink
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.
2. Kaakkola S: Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. Drugs. 2000 Jun;59(6):1233-50.
3. 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.
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.
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.
6. https://www.ncbi.nlm.nih.gov/pubmed/?term=20381177
7. https://www.ncbi.nlm.nih.gov/pubmed/?term=20502133
8. https://www.ncbi.nlm.nih.gov/pubmed/?term=21521027
9. https://www.ncbi.nlm.nih.gov/pubmed/?term=22136163