TOLCAPONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H11NO5
Molecular Weight	273.2408
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=CC=C(C=C1)C(=O)C2=CC(O)=C(O)C(=C2)[N+]([O-])=O

InChI

InChIKey=MIQPIUSUKVNLNT-UHFFFAOYSA-N

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

HIDE SMILES / InChI

Molecular Formula	C14H11NO5
Molecular Weight	273.2408
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: http://www.drugbank.ca/drugs/DB00323
Curator's Comment: Description was created based on several sources, including

Tolcapone is a potent, selective, and reversible inhibitor of catechol-O-methyltransferase (COMT). In humans, COMT is distributed throughout various organs. COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. COMT is responsible for the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa catalyzing it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery. When tolcapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. 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 in patients as well as increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa. 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, resulting in an increase in plasma levodopa concentrations. The inhibition of COMT also causes a reduction in circulating 3-OMD as a result of decreased peripheral metabolism of levodopa. This may lead to an increase distribution of levodopa into the CNS through the reduction of its competitive substrate, 3-OMD, for transport mechanisms. Sustained levodopa concentrations presumably result in more consistent dopaminergic stimulation, resulting in greater reduction in the manifestations of parkinsonian syndrome. Tolcapone is used 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. Tolcapone is sold under the brand name Tasmar.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Catechol O-methyltransferase 21 Target ID: CHEMBL2023 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	Inhibitor 8504		151.0 nM [IC50]
NCI-H1299 3 Target ID: CHEMBL612255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24148818	Inhibitor 8504		29.3 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Idiopathic Parkinson's disease 19 Sources: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	Secondary		Approved 8583	Tasmar Approved Use TASMAR is indicated as an adjunct to levodopa and carbidopa for the treatment of the signs and symptoms of idiopathic Parkinson’s disease. Because of the risk of potentially fatal, acute fulminant liver failure, TASMAR (tolcapone) should ordinarily be used in patients with Parkinson’s disease on l-dopa/carbidopa who are experiencing symptom fluctuations and are not responding satisfactorily to or are not appropriate candidates for other adjunctive therapies. Because of the risk of liver injury and because TASMAR, when it is effective, provides an observable symptomatic benefit, the patient who fails to show substantial clinical benefit within 3 weeks of initiation of treatment, should be withdrawn from TASMAR. Launch Date 1998

C_max

Value	Dose	Analyte	Population
0.3 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
0.7 mg/L REVIEW https://pubmed.ncbi.nlm.nih.gov/7768073	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.3 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.4 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
4.6 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
6.3 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
13.4 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
20.3 mg/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

AUC

Value	Dose	Analyte	Population
0.5 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.1 mg × h/L REVIEW https://pubmed.ncbi.nlm.nih.gov/7768073	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.8 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
5.7 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
12.2 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
18.5 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
43.8 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
67.7 mg × h/L EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
1.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	5 mg single, oral dose: 5 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.7 h REVIEW https://pubmed.ncbi.nlm.nih.gov/7768073	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	25 mg single, oral dose: 25 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
1.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	50 mg single, oral dose: 50 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	100 mg single, oral dose: 100 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED
2.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	400 mg single, oral dose: 400 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
3.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/7768073	800 mg single, oral dose: 800 mg route of administration: Oral experiment type: SINGLE co-administered:	TOLCAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
0.1% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unknown, unknown		TOLCAPONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
800 mg 3 times / day multiple, oral Overdose Dose: 800 mg, 3 times / day Route: oral Route: multiple Dose: 800 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf https://pubmed.ncbi.nlm.nih.gov/9333106	healthy, 55 - 75 Health Status: healthy Age Group: 55 - 75 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf https://pubmed.ncbi.nlm.nih.gov/9333106	Disc. AE: Nausea, Vomiting... AEs leading to discontinuation/dose reduction: Nausea (severe, 33%) Vomiting (severe, 33%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf https://pubmed.ncbi.nlm.nih.gov/9333106
800 mg 3 times / day multiple, oral Overdose Dose: 800 mg, 3 times / day Route: oral Route: multiple Dose: 800 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	healthy Health Status: healthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	Disc. AE: Dizziness... AEs leading to discontinuation/dose reduction: Dizziness Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf
200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	Disc. AE: Acute liver failure, Hepatocellular injury... AEs leading to discontinuation/dose reduction: Acute liver failure (grade 3-5) Hepatocellular injury (grade 3-5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf
200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	Disc. AE: Diarrhea... AEs leading to discontinuation/dose reduction: Diarrhea (6%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf
200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	Disc. AE: ALT increased, Aspartate aminotransferase increased... AEs leading to discontinuation/dose reduction: ALT increased (1.7%) Aspartate aminotransferase increased (1.7%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf
200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	Disc. AE: Somnolence... AEs leading to discontinuation/dose reduction: Somnolence (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf
200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	Disc. AE: Hallucinations... AEs leading to discontinuation/dose reduction: Hallucinations (1%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf

AEs

AE	Significance	Dose	Population
Nausea	severe, 33% Disc. AE	800 mg 3 times / day multiple, oral Overdose Dose: 800 mg, 3 times / day Route: oral Route: multiple Dose: 800 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf https://pubmed.ncbi.nlm.nih.gov/9333106	healthy, 55 - 75 Health Status: healthy Age Group: 55 - 75 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf https://pubmed.ncbi.nlm.nih.gov/9333106
Vomiting	severe, 33% Disc. AE	800 mg 3 times / day multiple, oral Overdose Dose: 800 mg, 3 times / day Route: oral Route: multiple Dose: 800 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf https://pubmed.ncbi.nlm.nih.gov/9333106	healthy, 55 - 75 Health Status: healthy Age Group: 55 - 75 Sex: M+F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf https://pubmed.ncbi.nlm.nih.gov/9333106
Dizziness	Disc. AE	800 mg 3 times / day multiple, oral Overdose Dose: 800 mg, 3 times / day Route: oral Route: multiple Dose: 800 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	healthy Health Status: healthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf
Acute liver failure	grade 3-5 Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf
Hepatocellular injury	grade 3-5 Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf
Diarrhea	6% Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf
ALT increased	1.7% Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf
Aspartate aminotransferase increased	1.7% Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf
Somnolence	1% Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf
Hallucinations	1% Disc. AE	200 mg 3 times / day multiple, oral Recommended Dose: 200 mg, 3 times / day Route: oral Route: multiple Dose: 200 mg, 3 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2013/020697s004lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	inhibitor 2438	inhibitor 2507

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP3A 227 CYP2A6 879 CYP1A2 2153 CYP2C19 2057	CYP2A6 626

Drug as perpetrator

Target	Modality	Activity	Clinical evidence
CYP2C19 2141	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20697_Tasmar_pharmr_P4.pdf#page=27 Page: 27.0	no
CYP2D6 2546	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20697_Tasmar_pharmr_P4.pdf#page=27 Page: 27.0	no
CYP2A6 911	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20697_Tasmar_pharmr_P4.pdf#page=27 Page: 27.0	yes [Ki 21 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20697_Tasmar_pharmr_P4.pdf#page=27 Page: 27.0	yes [Ki 30 uM]
CYP3A 317	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20697_Tasmar_pharmr_P4.pdf#page=27 Page: 27.0	yes [Ki 49 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20697_Tasmar_pharmr_P1.pdf#page=12 Page: 12.0	yes [Ki 7.4 uM]	yes (co-administration study) Comment: co-administration of tolcapone did not change the pharmakokinetics of tolcapone Sources: https://www.accessdata.fda.gov/drugsatfda_docs/nda/98/20697_Tasmar_pharmr_P1.pdf#page=12 Page: 12.0

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1946	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020697s013s015lbl.pdf#page=4 Page: 4.0	yes [Km 7 uM]
CYP2A6 626	substrate 4014 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020697s013s015lbl.pdf#page=4 Page: 4.0	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:63630	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:63630
ChemicalBook	CB9302569	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB9302569
eMolecules	2735694	https://www.emolecules.com/cgi-bin/more?vid=2735694
MolPort	MolPort-003-850-570	https://www.molport.com/shop/molecule-link/MolPort-003-850-570
Selleck Chemicals	tolcapone	http://www.selleckchem.com/products/tolcapone.html
ZINC	ZINC000035342789	http://zinc15.docking.org/substances/ZINC000035342789

PubMed

Title	Date	PubMed
Safety and tolerability of adjunctive tolcapone treatment in patients with early Parkinson's disease.	2007-09	17098835
Tolcapone improves cognition and cortical information processing in normal human subjects.	2007-05	17063156
The endophenotype concept in psychiatric genetics.	2007-02	16978446
Entacapone to tolcapone switch: Multicenter double-blind, randomized, active-controlled trial in advanced Parkinson's disease.	2007-01	17089403
Treatment of cognitive deficits associated with schizophrenia: potential role of catechol-O-methyltransferase inhibitors.	2007	17579498
Tolcapone in the management of Parkinson's disease.	2006-11	17059382
Bioactivation and hepatotoxicity of nitroaromatic drugs.	2006-10	17073576
Tolcapone decreases plasma levels of S-adenosyl-L-homocysteine and homocysteine in treated Parkinson's disease patients.	2006-06	16758261
Practice Parameter: treatment of Parkinson disease with motor fluctuations and dyskinesia (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology.	2006-04-11	16606909
Tolcapone: new drug. In Parkinson's disease: unacceptable risk of severe hepatitis.	2006-04	16604736
Optimal design for multivariate response pharmacokinetic models.	2006-04	16550455
Increased catechol-O-methyltransferase activity and protein expression in OX-42-positive cells in the substantia nigra after lipopolysaccharide microinfusion.	2006-03-23	17573159
Pharmacokinetic optimisation in the treatment of Parkinson's disease : an update.	2006	16485914
[Comparison of the safety of the medicinal product in the European Union and the United States, tolcapone (Tasmar) -- COMT inhibitor as the analyzed example].	2005-12-16	16355307
Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism.	2005-12-13	16344532
[Serious tolpcapone-induced hepatitis 17 months after commencing treatment].	2005-11	16288178
Transcriptional and behavioral interaction between 22q11.2 orthologs modulates schizophrenia-related phenotypes in mice.	2005-11	16234811
Rapid simultaneous determination of metabolic clearance of multiple compounds catalyzed in vitro by recombinant human UDP-glucuronosyltransferases.	2005-06-01	15866534
The effect of nicotine in combination with various dopaminergic drugs on nigrostriatal dopamine in rats.	2005-06	16012872
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005-06	15962942
Evidence-based medical review update: pharmacological and surgical treatments of Parkinson's disease: 2001 to 2004.	2005-05	15818599
The role of physicochemical properties of entacapone and tolcapone on their efficacy during local intrastriatal administration.	2005-04	15784340
Tolcapone in Parkinson's disease: liver toxicity and clinical efficacy.	2005-01	15709899
[Tolcapone treatment of late stages of Parkinson's disease].	2005	15984185
Oxidative stress mediated idiosyncratic drug toxicity.	2005	15931767
Role of COMT inhibitors and dopamine agonists in the treatment of motor fluctuations.	2005	15822107
Tolcapone: a review of its use in the management of Parkinson's disease.	2005	15697329
The combination of liquid chromatography/tandem mass spectrometry and chip-based infusion for improved screening and characterization of drug metabolites.	2005	15685686
Synthesis, biological evaluation, and molecular modeling studies of a novel, peripherally selective inhibitor of catechol-O-methyltransferase.	2004-12-02	15566291
Assessment of catechol induction and glucuronidation in rat liver microsomes.	2004-12	15371300
Catechol-O-methyltransferase inhibitors for levodopa-induced complications in Parkinson's disease.	2004-10-18	15495119
Catechol-O-methyltransferase inhibitors versus active comparators for levodopa-induced complications in Parkinson's disease.	2004-10-18	15495118
Clinical advantages of COMT inhibition with entacapone - a review.	2004-10	15340869
SL25.1131 [3(S),3a(S)-3-methoxymethyl-7-[4,4,4-trifluorobutoxy]-3,3a,4,5-tetrahydro-1,3-oxazolo[3,4-a]quinolin-1-one], a new, reversible, and mixed inhibitor of monoamine oxidase-A and monoamine oxidase-B: biochemical and behavioral profile.	2004-09	15178694
Catechol-o-methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex.	2004-06-09	15190105
[Treatment in Parkinson disease].	2004-04-11	15188639
Differences in toxicity of the catechol-O-methyl transferase inhibitors, tolcapone and entacapone to cultured human neuroblastoma cells.	2004-03	14975680
Safety and tolerability of COMT inhibitors.	2004-01-13	14718679
[A comparative study of efficacy of dopamine receptors agonists and catechol-O-methyltransferase in the treatment of late stages of Parkinson's disease].	2004	14870689
Cerebrospinal fluid 3,4-dihydroxyphenylacetic acid level after tolcapone administration as an indicator of nigrostriatal degeneration.	2003-09	12957500
Prevention and treatment of motor fluctuations.	2003-08	12915071
Modifications of plasma and platelet levels of L-DOPA and its direct metabolites during treatment with tolcapone or entacapone in patients with Parkinson's disease.	2003-08	12898346
Tissue histopathology, clinical chemistry and behaviour of adult Comt-gene-disrupted mice.	2003-07-29	12884403
The psychometric properties of the Parkinson's Impact Scale (PIMS) as a measure of quality of life in Parkinson's disease.	2003-06	12781596
Hepatotoxic profile of catechol-O-methyltransferase inhibitors in Parkinson's disease.	2003-05	12904105
Molecular modeling and metabolic studies of the interaction of catechol-O-methyltransferase and a new nitrocatechol inhibitor.	2003-03	12584150
The relevance of preclinical studies for the treatment of Parkinson's disease.	2003-02	12761633
In vitro metabolism of tolcapone to reactive intermediates: relevance to tolcapone liver toxicity.	2003-02	12588182
Tolcapone-related liver dysfunction: implications for use in Parkinson's disease therapy.	2003	12908845
Advances in the pharmacological management of Parkinson disease.	2003	12830929

Patents

Sample Use Guides

In Vivo Use Guide

The initial dose of TASMAR is always 100 mg three times per day. The recommended daily dose of TASMAR is also 100 mg tid.

Route of Administration: Oral

In Vitro Use Guide

When using a fixed amount of total protein (2 ug/ml), but variable concentrations of COMT, the inhibitory potency of tolcapone upon S- and MB-COMT activity in the rat brain was in the low nM range (IC50's of 2 and 3 nM, respectively), whereas in rat liver the IC50 values for tolcapone against liver MB- and S-COMT (IC50's of 123 and 795 nM, respectively) were markedly higher than those observed in the brain. By contrast, when inhibition studies were performed with a fixed concentration of COMT (15 nM), tolcapone was found to be endowed with the same potency (in the low nM range) in inhibiting S- and MB-COMT from both brain and liver.

Substance Class	Chemical Created by `admin` on `Wed Apr 02 09:33:04 GMT 2025` Edited by `admin` on `Wed Apr 02 09:33:04 GMT 2025`
Record UNII	CIF6334OLY
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TOLCAPONE

Official Name

English

TASMAR

Preferred Name

English

Tolcapone [WHO-DD]

Common Name

English

RO-407592

Code

English

TOLCAPONE [USP MONOGRAPH]

Common Name

English

TOLCAPONE [MI]

Common Name

English

TOLCAPONE [MART.]

Common Name

English

TOLCAPONE [ORANGE BOOK]

Common Name

English

TOLCAPONE [USAN]

Common Name

English

RO-40-7592

Code

English

TOLCAPONE [JAN]

Common Name

English

TOLCAPONE [EMA EPAR]

Common Name

English

RO 40-7592

Code

English

3,4-DIHYDROXY-4'-METHYL-5-NITROBENZOPHENONE

Systematic Name

English

tolcapone [INN]

Common Name

English

TOLCAPONE [VANDF]

Common Name

English

TOLCAPONE [USP-RS]

Common Name

English

METHANONE, (3,4-DIHYDROXY-5-NITROPHENYL)(4-METHYLPHENYL)-

Systematic Name

English

Classification Tree Code System Code

EMA ASSESSMENT REPORTS

TASMAR (AUTHORIZED: PARKINSON DISEASE)