tolcapone ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
catechol-O-methyltransferase (COMT) inhibitors 2697 134308-13-7

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • RO 40-7592
  • tolcapone
  • tasmar
Tolcapone is a selective and reversible inhibitor of catechol-O-methyltransferase (COMT). The precise mechanism of action of tolcapone is unknown, but it is believed to be related to its ability to inhibit COMT and alter the plasma pharmacokinetics of levodopa. It is believed that these sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson's disease patients.
  • Molecular weight: 273.24
  • Formula: C14H11NO5
  • CLOGP: 3.25
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 2
  • TPSA: 103.35
  • ALOGS: -3.68
  • ROTB: 3

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
0.45 g O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 2 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 0.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 12.20 ยตM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 62 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.12 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1.90 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.00 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1.10 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Jan. 29, 1998 FDA VALEANT PHARMS LLC

FDA Adverse Event Reporting System (Female)

None

FDA Adverse Event Reporting System (Male)

None

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Hyperkinesia 57.33 51.42 10 297 2536 64495889

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N04BX01 NERVOUS SYSTEM
ANTI-PARKINSON DRUGS
DOPAMINERGIC AGENTS
Other dopaminergic agents
MeSH PA D018726 Anti-Dyskinesia Agents
MeSH PA D000978 Antiparkinson Agents
MeSH PA D065098 Catechol O-Methyltransferase Inhibitors
MeSH PA D002491 Central Nervous System Agents
MeSH PA D004791 Enzyme Inhibitors
FDA MoA N0000175756 Catechol O-Methyltransferase Inhibitors
FDA EPC N0000175757 Catechol-O-Methyltransferase Inhibitor
CHEBI has role CHEBI:48406 catechol O-methyltransferase inhibitors
CHEBI has role CHEBI:48407 antiparkinson agent

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Parkinson's disease indication 49049000 DOID:14330
Hallucinations contraindication 7011001
Low blood pressure contraindication 45007003
Tardive dyskinesia contraindication 102449007
Liver function tests abnormal contraindication 166603001
Disease of liver contraindication 235856003 DOID:409
Rhabdomyolysis contraindication 240131006
Malignant melanoma contraindication 372244006
Severe diarrhea contraindication 409587002
Breastfeeding (mother) contraindication 413712001




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 4.84 acidic
pKa2 9.54 acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Catechol O-methyltransferase Enzyme INHIBITOR Ki 9.57 SCIENTIFIC LITERATURE CHEMBL
G-protein coupled receptor 35 GPCR EC50 5.13 CHEMBL
Transthyretin Secreted Kd 7.69 CHEMBL
Krueppel-like factor 10 Nuclear other IC50 4.30 CHEMBL
Catechol O-methyltransferase Enzyme IC50 8.66 CHEMBL
Bile salt export pump Transporter IC50 4.33 CHEMBL
Genome polyprotein [Cleaved into: Capsid protein C Enzyme IC50 6.19 CHEMBL

External reference:

IDSource
4021095 VUID
N0000148551 NUI
D00786 KEGG_DRUG
4021095 VANDF
C0246330 UMLSCUI
CHEBI:63630 CHEBI
TCW PDB_CHEM_ID
CHEMBL1324 ChEMBL_ID
DB00323 DRUGBANK_ID
D000077867 MESH_DESCRIPTOR_UI
4659569 PUBCHEM_CID
6646 IUPHAR_LIGAND_ID
6873 INN_ID
CIF6334OLY UNII
153657 RXNORM
11535 MMSL
234124 MMSL
5597 MMSL
d04282 MMSL
007040 NDDF
108464002 SNOMEDCT_US
386851002 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Tasmar HUMAN PRESCRIPTION DRUG LABEL 1 0187-0938 TABLET, FILM COATED 100 mg ORAL NDA 27 sections
TOLCAPONE HUMAN PRESCRIPTION DRUG LABEL 1 50742-193 TABLET 100 mg ORAL ANDA 14 sections
Tolcapone HUMAN PRESCRIPTION DRUG LABEL 1 68682-938 TABLET, FILM COATED 100 mg ORAL NDA authorized generic 26 sections