ENTACAPONE

Details

Stereochemistry	ACHIRAL
Molecular Formula	C14H15N3O5
Molecular Weight	305.286
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	1
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN(CC)C(=O)C(\C#N)=C\C1=CC(=C(O)C(O)=C1)[N+]([O-])=O

InChI

InChIKey=JRURYQJSLYLRLN-BJMVGYQFSA-N

InChI=1S/C14H15N3O5/c1-3-16(4-2)14(20)10(8-15)5-9-6-11(17(21)22)13(19)12(18)7-9/h5-7,18-19H,3-4H2,1-2H3/b10-5+

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00494
Curator's Comment: Description was created based on several sources, including http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000171/WC500033075.pdf

Entacapone is a selective, reversible catechol-O-methyl transferase (COMT) inhibitor for the treatment of Parkinson's disease. It is a member of the class of nitrocatechols. When administered concomittantly with levodopa and a decarboxylase inhibitor (e.g., carbidopa), increased and more sustained plasma levodopa concentrations are reached as compared to the administration of levodopa and a decarboxylase inhibitor. The mechanism of action of entacapone is believed to be through its ability to inhibit COMT in peripheral tissues, altering the plasma pharmacokinetics of levodopa. When entacapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are greater and more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that at a given frequency of levodopa administration, these more sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to a greater reduction in the manifestations of parkinsonian syndrome. Entacapone is used as an adjunct to levodopa / carbidopa in the symptomatic treatment of patients with idiopathic Parkinson's Disease who experience the signs and symptoms of end-of-dose "wearing-off".

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Catechol O-methyltransferase 21 Target ID: CHEMBL2023 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9681662	Inhibitor 8297	151.0 nM [IC50]
NCI-H1299 3 Target ID: CHEMBL612255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24148818	Inhibitor 8297	76.8 µM [IC50]
Mycobacterium tuberculosis 21 Target ID: CHEMBL360 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19578428	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Parkinson's disease 226 Sources: https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/comtan.pdf	Secondary		Approved 8429	Comtan Approved Use Comtan is indicated as an adjunct to levodopa and carbidopa to treat end-of-dose “wearing-off” in patients with Parkinson’s disease Launch Date 9.4020482E11

C_max

Value	Dose	Co-administered	Analyte	Population
1095 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10492060	200 mg 10 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: LEVODOPA\|CARBIDOPA	LEVODOPA\|CARBIDOPA	ENTACAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1325 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10492060	200 mg 8 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered: LEVODOPA\|CARBIDOPA	LEVODOPA\|CARBIDOPA	ENTACAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1.2 μg/mL DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020796s15lbl.pdf	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered: LEVODOPA\|CARBIDOPA	LEVODOPA\|CARBIDOPA	ENTACAPONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1989 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10492060	200 mg 10 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: LEVODOPA\|CARBIDOPA	LEVODOPA\|CARBIDOPA	ENTACAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
2084 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10492060	200 mg 8 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered: LEVODOPA\|CARBIDOPA	LEVODOPA\|CARBIDOPA	ENTACAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

T_1/2

Value	Dose	Co-administered	Analyte	Population
1.8 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10492060	200 mg 10 times / day steady-state, oral dose: 200 mg route of administration: Oral experiment type: STEADY-STATE co-administered: LEVODOPA\|CARBIDOPA	LEVODOPA\|CARBIDOPA	ENTACAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED
1.3 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/10492060	200 mg 8 times / day multiple, oral dose: 200 mg route of administration: Oral experiment type: MULTIPLE co-administered: LEVODOPA\|CARBIDOPA	LEVODOPA\|CARBIDOPA	ENTACAPONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/020796s15lbl.pdf			ENTACAPONE plasma	Homo sapiens population: UNKNOWN age: UNKNOWN sex: UNKNOWN food status: UNKNOWN

Doses

Dose	Population	Adverse events
25 mg single, intravenous Dose: 25 mg Route: intravenous Route: single Dose: 25 mg Sources: https://pubmed.ncbi.nlm.nih.gov/8039535	healthy, 24 years (range: 22-28 years) n = 12 Health Status: healthy Age Group: 24 years (range: 22-28 years) Sex: M Population Size: 12 Sources: https://pubmed.ncbi.nlm.nih.gov/8039535	Sources: https://pubmed.ncbi.nlm.nih.gov/8039535
2400 mg 1 times / day steady, oral Highest studied dose Dose: 2400 mg, 1 times / day Route: oral Route: steady Dose: 2400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	healthy n = 8 Health Status: healthy Population Size: 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	Other AEs: Abdominal pain, Loose stools... Other AEs: Abdominal pain Loose stools Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF
2400 mg 1 times / day steady, oral Highest studied dose Dose: 2400 mg, 1 times / day Route: oral Route: steady Dose: 2400 mg, 1 times / day Co-administed with:: levodopa/carbidopa(14 days) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	unhealthy n = 15 Health Status: unhealthy Condition: Parkinson’s Disease Population Size: 15 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	Other AEs: Abdominal pain, Loose stools... Other AEs: Abdominal pain Loose stools Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF
800 mg single, oral Highest studied dose Dose: 800 mg Route: oral Route: single Dose: 800 mg Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	unhealthy Health Status: unhealthy Condition: Parkinson’s Disease Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF
200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	unhealthy n = 603 Health Status: unhealthy Condition: Parkinson’s Disease Population Size: 603 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	Disc. AE: Psychiatric symptom, Diarrhea... AEs leading to discontinuation/dose reduction: Psychiatric symptom (2%) Diarrhea (2%) Dyskinesia (2%) Nausea (2%) Abdominal pain (1%) Hyperkinesia (2%) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF

AEs

AE	Significance	Dose	Population
Abdominal pain		2400 mg 1 times / day steady, oral Highest studied dose Dose: 2400 mg, 1 times / day Route: oral Route: steady Dose: 2400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	healthy n = 8 Health Status: healthy Population Size: 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF
Loose stools		2400 mg 1 times / day steady, oral Highest studied dose Dose: 2400 mg, 1 times / day Route: oral Route: steady Dose: 2400 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	healthy n = 8 Health Status: healthy Population Size: 8 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF
Abdominal pain		2400 mg 1 times / day steady, oral Highest studied dose Dose: 2400 mg, 1 times / day Route: oral Route: steady Dose: 2400 mg, 1 times / day Co-administed with:: levodopa/carbidopa(14 days) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	unhealthy n = 15 Health Status: unhealthy Condition: Parkinson’s Disease Population Size: 15 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF
Loose stools		2400 mg 1 times / day steady, oral Highest studied dose Dose: 2400 mg, 1 times / day Route: oral Route: steady Dose: 2400 mg, 1 times / day Co-administed with:: levodopa/carbidopa(14 days) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	unhealthy n = 15 Health Status: unhealthy Condition: Parkinson’s Disease Population Size: 15 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF
Abdominal pain	1% Disc. AE	200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	unhealthy n = 603 Health Status: unhealthy Condition: Parkinson’s Disease Population Size: 603 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF
Diarrhea	2% Disc. AE	200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	unhealthy n = 603 Health Status: unhealthy Condition: Parkinson’s Disease Population Size: 603 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF
Dyskinesia	2% Disc. AE	200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	unhealthy n = 603 Health Status: unhealthy Condition: Parkinson’s Disease Population Size: 603 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF
Hyperkinesia	2% Disc. AE	200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	unhealthy n = 603 Health Status: unhealthy Condition: Parkinson’s Disease Population Size: 603 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF
Nausea	2% Disc. AE	200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	unhealthy n = 603 Health Status: unhealthy Condition: Parkinson’s Disease Population Size: 603 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF
Psychiatric symptom	2% Disc. AE	200 mg 1 times / day steady, oral Recommended Dose: 200 mg, 1 times / day Route: oral Route: steady Dose: 200 mg, 1 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF	unhealthy n = 603 Health Status: unhealthy Condition: Parkinson’s Disease Population Size: 603 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/1999/20796LBL.PDF

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4798	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4798
ChemicalBook	CB5726435	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB5726435
MolPort	MolPort-003-847-054	https://www.molport.com/shop/molecule-link/MolPort-003-847-054
Selleck Chemicals	entacapone	http://www.selleckchem.com/products/entacapone.html
ZINC	ZINC000035342787	http://zinc15.docking.org/substances/ZINC000035342787
eMolecules	27345033	https://www.emolecules.com/cgi-bin/more?vid=27345033

PubMed

Title	Date	PubMed
Beneficial effects of co-administration of catechol-O-methyltransferase inhibitors and L-dihydroxyphenylalanine in rat models of depression.	1995 Feb 14	7768276
Alterations in preproenkephalin and adenosine-2a receptor mRNA, but not preprotachykinin mRNA correlate with occurrence of dyskinesia in normal monkeys chronically treated with L-DOPA.	2000 Mar	10762340
Entacapone.	2000 Sep	10981253
Efficacy and safety of entacapone in Parkinson's disease patients with suboptimal levodopa response: a 6-month randomized placebo-controlled double-blind study in Germany and Austria (Celomen study).	2002 Apr	11939936
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 Aug	12898346
Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson's disease: a randomised, placebo controlled, double blind, six month study.	2003 Aug	12876237
Sleep attacks in Parkinson's disease induced by Entacapone, a COMT-inhibitor.	2003 Feb	12588639
An artist's view of drug-induced hallucinosis.	2003 Jul	12815666
An active and water-soluble truncation mutant of the human UDP-glucuronosyltransferase 1A9.	2004 Apr	15044611
Synthesis, biological evaluation, and molecular modeling studies of a novel, peripherally selective inhibitor of catechol-O-methyltransferase.	2004 Dec 2	15566291
Entacapone increases and prolongs the central effects of l-DOPA in the 6-hydroxydopamine-lesioned rat.	2004 Nov	15502970
Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism.	2005 Dec 13	16344532
Kinetic characterization of the 1A subfamily of recombinant human UDP-glucuronosyltransferases.	2005 Jul	15802387
Prediction of genotoxicity of chemical compounds by statistical learning methods.	2005 Jun	15962942
Coadministration of entacapone with levodopa attenuates the severity of dyskinesias in hemiparkinsonian rats.	2006 May	16437585
Entacapone to tolcapone switch: Multicenter double-blind, randomized, active-controlled trial in advanced Parkinson's disease.	2007 Jan	17089403
Novel screening assay for antioxidant protection against peroxyl radical-induced loss of protein function.	2007 Nov	17705259
Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes.	2008 Dec	18722529
Levodopa/carbidopa/entacapone-induced acute Pisa syndrome in a Parkinson's disease patient.	2008 Dec 15	18814889
Remission of acute psychotic anxious depression in a patient with Parkinson's disease after treatment with quetiapine.	2009 Dec 15	19890998
Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of alpha-synuclein and beta-amyloid and protect against amyloid-induced toxicity.	2010 May 14	20150427

Patents

Sample Use Guides

In Vivo Use Guide

The recommended dose of Comtan (entacapone) is one 200 mg tablet administered concomitantly with each levodopa and carbidopa dose to a maximum of 8 times daily (200 mg x 8 = 1,600 mg per day). Comtan should always be administered in association with levodopa and carbidopa. Entacapone has no antiparkinsonian effect of its own.

Route of Administration: Oral

In Vitro Use Guide

Kinetic assays indicate that Comtan inhibits InhA activity by 47.0% at an entacapone concentration of approximately 80 uM.

Name

Type

Language

ENTACAPONE

Official Name

English

OR-611

Code

English

Entacapone [WHO-DD]

Common Name

English

ENTACAPONE [EP MONOGRAPH]

Common Name

English

COMTAN

Brand Name

English

COMTESS

Brand Name

English

CORBILTA COMPONENT ENTACAPONE

Brand Name

English

ENTACAPONE [ORANGE BOOK]

Common Name

English

ENTACAPONE [JAN]

Common Name

English

ENTACAPONE COMPONENT OF STALEVO

Brand Name

English

ENTACAPONE COMPONENT OF CORBILTA

Brand Name

English

ENTACAPONE [MI]

Common Name

English

ENTACAPONE COMPONENT OF LEVODOPA/CARBIDOPA/ENTACAPONE ORION

Brand Name

English

ENTACAPONE [USP-RS]

Common Name

English

entacapone [INN]

Common Name

English

(E)-.ALPHA.-CYANO-N,N-DIETHYL-3,4-DIHYDROXY-5-NITROCINNAMAMIDE

Systematic Name

English

ENTACAPONE [MART.]

Common Name

English

LEVODOPA/CARBIDOPA/ENTACAPONE ORION COMPONENT ENTACAPONE

Brand Name

English

ENTACAPONE [EMA EPAR]

Common Name

English

ENTACAPONE [USP MONOGRAPH]

Common Name

English

STALEVO COMPONENT ENTACAPONE

Brand Name

English

ENTACAPONE [USAN]

Common Name

English

ENTACAPONE [VANDF]

Common Name

English

ENTACAPONE TEVA

Brand Name

English

ENTACAPONE ORION

Brand Name

English

2-PROPENAMIDE, 2-CYANO-3-(3,4-DIHYDROXY-5-NITROPHENYL)-N,N-DIETHYL-

Systematic Name

English

Classification Tree Code System Code

NDF-RT

N0000175756