U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C14H15N3O5
Molecular Weight 305.2865
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 1
Charge 0

SHOW SMILES / InChI
Structure of ENTACAPONE

SMILES

CCN(CC)C(=O)/C(=C(\[H])/c1cc(c(c(c1)O)O)N(=O)=O)/C#N

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

Molecular Formula C14H15N3O5
Molecular Weight 305.2865
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 1
Optical Activity NONE

Description
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

Curator's Comment:: In animals, while entacapone enters the central nervous system (CNS) to a minimal extent, it has been shown to inhibit central COMT activity. In humans penetration of entacapone into the CNS is poor http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Scientific_Discussion/human/000171/WC500033075.pdf

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
151.0 nM [IC50]
76.8 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Secondary
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
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
1095 ng/mL
200 mg 10 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: LEVODOPA|CARBIDOPA
ENTACAPONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
1325 ng/mL
200 mg 8 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: LEVODOPA|CARBIDOPA
ENTACAPONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
1.2 μg/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered: LEVODOPA|CARBIDOPA
ENTACAPONE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
1989 ng × h/mL
200 mg 10 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: LEVODOPA|CARBIDOPA
ENTACAPONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
2084 ng × h/mL
200 mg 8 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: LEVODOPA|CARBIDOPA
ENTACAPONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
1.8 h
200 mg 10 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered: LEVODOPA|CARBIDOPA
ENTACAPONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
1.3 h
200 mg 8 times / day multiple, oral
dose: 200 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered: LEVODOPA|CARBIDOPA
ENTACAPONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: MALE
food status: FED
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
ENTACAPONE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
25 mg single, intravenous
Dose: 25 mg
Route: intravenous
Route: single
Dose: 25 mg
Sources:
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:
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:
healthy
n = 8
Health Status: healthy
Population Size: 8
Sources:
Other AEs: Abdominal pain, 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:
unhealthy
n = 15
Health Status: unhealthy
Condition: Parkinson’s Disease
Population Size: 15
Sources:
Other AEs: Abdominal pain, Loose stools...
800 mg single, oral
Highest studied dose
Dose: 800 mg
Route: oral
Route: single
Dose: 800 mg
Sources:
unhealthy
Health Status: unhealthy
Condition: Parkinson’s Disease
Sources:
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:
unhealthy
n = 603
Health Status: unhealthy
Condition: Parkinson’s Disease
Population Size: 603
Sources:
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:
AEs

AEs

AESignificanceDosePopulation
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:
healthy
n = 8
Health Status: healthy
Population Size: 8
Sources:
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:
healthy
n = 8
Health Status: healthy
Population Size: 8
Sources:
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:
unhealthy
n = 15
Health Status: unhealthy
Condition: Parkinson’s Disease
Population Size: 15
Sources:
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:
unhealthy
n = 15
Health Status: unhealthy
Condition: Parkinson’s Disease
Population Size: 15
Sources:
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:
unhealthy
n = 603
Health Status: unhealthy
Condition: Parkinson’s Disease
Population Size: 603
Sources:
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:
unhealthy
n = 603
Health Status: unhealthy
Condition: Parkinson’s Disease
Population Size: 603
Sources:
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:
unhealthy
n = 603
Health Status: unhealthy
Condition: Parkinson’s Disease
Population Size: 603
Sources:
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:
unhealthy
n = 603
Health Status: unhealthy
Condition: Parkinson’s Disease
Population Size: 603
Sources:
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:
unhealthy
n = 603
Health Status: unhealthy
Condition: Parkinson’s Disease
Population Size: 603
Sources:
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:
unhealthy
n = 603
Health Status: unhealthy
Condition: Parkinson’s Disease
Population Size: 603
Sources:
PubMed

PubMed

TitleDatePubMed
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
Entacapone.
2000 Sep
L-dopa induces dyskinesia in normal monkeys: behavioural and pharmacokinetic observations.
2001 Aug
Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson's disease.
2001 Jun
Long-term comparative experience with tolcapone and entacapone in advanced Parkinson's disease.
2001 Sep-Oct
Sleep attacks in Parkinson's disease induced by Entacapone, a COMT-inhibitor.
2003 Feb
Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat.
2003 Feb
An artist's view of drug-induced hallucinosis.
2003 Jul
Prediction of genotoxicity of chemical compounds by statistical learning methods.
2005 Jun
Entacapone potentiates the long-duration response but does not normalize levodopa-induced molecular changes.
2008 Dec
Levodopa/carbidopa/entacapone-induced acute Pisa syndrome in a Parkinson's disease patient.
2008 Dec 15
[Treatment of Parkinson's disease at present and in the future].
2008 Nov
Drug discovery using chemical systems biology: repositioning the safe medicine Comtan to treat multi-drug and extensively drug resistant tuberculosis.
2009 Jul
Capture compound mass spectrometry sheds light on the molecular mechanisms of liver toxicity of two Parkinson drugs.
2010 Jan
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
Patents

Sample Use Guides

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
Kinetic assays indicate that Comtan inhibits InhA activity by 47.0% at an entacapone concentration of approximately 80 uM.
Substance Class Chemical
Created
by admin
on Fri Jun 25 21:14:23 UTC 2021
Edited
by admin
on Fri Jun 25 21:14:23 UTC 2021
Record UNII
4975G9NM6T
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
ENTACAPONE
EMA EPAR   EP   INN   JAN   MART.   MI   ORANGE BOOK   USAN   USP-RS   VANDF   WHO-DD  
INN   USAN  
Official Name English
OR-611
Code 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 [WHO-DD]
Common 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
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
EMA ASSESSMENT REPORTS STALEVO (AUTHORIZED: PARKINSON DISEASE)
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
NDF-RT N0000175757
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
EMA ASSESSMENT REPORTS CORBILTA (AUTHORIZED: NERVOUS SYSTEM DISEASES)
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
EMA ASSESSMENT REPORTS LEVODOPA/CARBIDOPA/ENTACAPONE ORION (AUTHORIZED: PARKINSON DISEASE)
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
EMA ASSESSMENT REPORTS COMTESS (AUTHORIZED: PARKINSON DISEASE)
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
LIVERTOX 352
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
EMA ASSESSMENT REPORTS ENTACAPONE ORION (AUTHORIZED: PARKINSON DISEASE)
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
EMA ASSESSMENT REPORTS CORBILTA (AUTHORIZED: PARKINSON DISEASE)
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
WHO-ATC N04BX02
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
EMA ASSESSMENT REPORTS ENTACAPONE TEVA (AUTHORIZED: PARKINSON DISEASE)
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
WHO-VATC QN04BX02
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
NCI_THESAURUS C38149
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
EMA ASSESSMENT REPORTS COMTAN (AUTHORIZED: PARKINSON DISEASE)
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
Code System Code Type Description
USP_CATALOG
1235933
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY USP-RS
DRUG CENTRAL
1018
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
INN
6812
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
MESH
C071192
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
EVMPD
SUB06552MIG
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
DRUG BANK
DB00494
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
RXCUI
60307
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY RxNorm
FDA UNII
4975G9NM6T
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
CAS
130929-57-6
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
IUPHAR
6647
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
WIKIPEDIA
ENTACAPONE
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
HSDB
8251
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
PUBCHEM
5281081
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
ChEMBL
CHEMBL953
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
MERCK INDEX
M4918
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY Merck Index
LACTMED
Entacapone
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
NCI_THESAURUS
C61746
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
EPA CompTox
130929-57-6
Created by admin on Fri Jun 25 21:14:23 UTC 2021 , Edited by admin on Fri Jun 25 21:14:23 UTC 2021
PRIMARY
Related Record Type Details
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
EP
BINDER->LIGAND
BINDING
TARGET -> INHIBITOR
BASIS OF STRENGTH->SUBSTANCE
ASSAY (HPLC)
USP
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METABOLITE -> PARENT
MAJOR
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METABOLITE -> PARENT
Active in vitro,but contribution should be little due to low plasma level
PLASMA
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IMPURITY -> PARENT
IMPURITY -> PARENT
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
USP
Related Record Type Details
ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Biological Half-life PHARMACOKINETIC
Volume of Distribution PHARMACOKINETIC