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
SMILES
CCN(CC)C(=O)C(=C/C1=CC(=C(O)C(O)=C1)[N+]([O-])=O)\C#N
InChI
InChIKey=JRURYQJSLYLRLN-YHYXMXQVSA-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-
Molecular Formula | C14H15N3O5 |
Molecular Weight | 305.286 |
Charge | 0 |
Count |
|
Stereochemistry | ACHIRAL |
Additional Stereochemistry | No |
Defined Stereocenters | 0 / 0 |
E/Z Centers | 1 |
Optical Activity | NONE |
DescriptionSources: http://www.drugbank.ca/drugs/DB00494Curator'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
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
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
Originator
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL2023 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9681662 |
151.0 nM [IC50] | ||
Target ID: CHEMBL612255 Sources: https://www.ncbi.nlm.nih.gov/pubmed/24148818 |
76.8 µM [IC50] | ||
Target ID: CHEMBL360 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19578428 |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Secondary | Comtan Approved UseComtan is indicated as an adjunct to levodopa and carbidopa to treat end-of-dose “wearing-off” in
patients with Parkinson’s disease Launch Date9.4020482E11 |
Cmax
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 |
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 |
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
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 |
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 |
ENTACAPONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
T1/2
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 |
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 |
ENTACAPONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: FED |
Funbound
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
2% |
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: |
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... Other AEs: Abdominal pain 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: |
Other AEs: Abdominal pain, Loose stools... Other AEs: Abdominal pain Sources: 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%) Sources: Diarrhea (2%) Dyskinesia (2%) Nausea (2%) Abdominal pain (1%) Hyperkinesia (2%) |
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: |
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
Title | Date | PubMed |
---|---|---|
Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. | 1995 Apr 4 |
|
Beneficial effects of co-administration of catechol-O-methyltransferase inhibitors and L-dihydroxyphenylalanine in rat models of depression. | 1995 Feb 14 |
|
Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. | 2000 Jun |
|
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 |
|
Efficacy and tolerability of entacapone as adjunctive therapy to levodopa in patients with Parkinson's disease and end-of-dose deterioration in daily medical practice: an open, multicenter study. | 2001 |
|
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 |
|
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 |
|
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 |
|
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 |
|
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 |
|
An active and water-soluble truncation mutant of the human UDP-glucuronosyltransferase 1A9. | 2004 Apr |
|
Synthesis, biological evaluation, and molecular modeling studies of a novel, peripherally selective inhibitor of catechol-O-methyltransferase. | 2004 Dec 2 |
|
Entacapone increases and prolongs the central effects of l-DOPA in the 6-hydroxydopamine-lesioned rat. | 2004 Nov |
|
Two patients with COMT inhibitor-induced hepatic dysfunction and UGT1A9 genetic polymorphism. | 2005 Dec 13 |
|
Kinetic characterization of the 1A subfamily of recombinant human UDP-glucuronosyltransferases. | 2005 Jul |
|
Prediction of genotoxicity of chemical compounds by statistical learning methods. | 2005 Jun |
|
Coadministration of entacapone with levodopa attenuates the severity of dyskinesias in hemiparkinsonian rats. | 2006 May |
|
Entacapone to tolcapone switch: Multicenter double-blind, randomized, active-controlled trial in advanced Parkinson's disease. | 2007 Jan |
|
Novel screening assay for antioxidant protection against peroxyl radical-induced loss of protein function. | 2007 Nov |
|
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 |
|
Remission of acute psychotic anxious depression in a patient with Parkinson's disease after treatment with quetiapine. | 2009 Dec 15 |
|
Drug discovery using chemical systems biology: repositioning the safe medicine Comtan to treat multi-drug and extensively drug resistant tuberculosis. | 2009 Jul |
|
Discovery of a long-acting, peripherally selective inhibitor of catechol-O-methyltransferase. | 2010 Apr 22 |
|
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 |
|
Mirtazapine-associated urinary retention. | 2010 Summer |
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
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/19578428
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
Edited
Fri Dec 15 17:23:57 UTC 2023
by
admin
on
Fri Dec 15 17:23:57 UTC 2023
|
Record UNII |
4X96VV9HUQ
|
Record Status |
Validated (UNII)
|
Record Version |
|
-
Download
Name | Type | Language | ||
---|---|---|---|---|
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English | ||
|
Common Name | English | ||
|
Systematic Name | English | ||
|
Common Name | English |
Code System | Code | Type | Description | ||
---|---|---|---|---|---|
|
1235944
Created by
admin on Fri Dec 15 17:23:57 UTC 2023 , Edited by admin on Fri Dec 15 17:23:57 UTC 2023
|
PRIMARY | |||
|
21864625
Created by
admin on Fri Dec 15 17:23:57 UTC 2023 , Edited by admin on Fri Dec 15 17:23:57 UTC 2023
|
PRIMARY | |||
|
4X96VV9HUQ
Created by
admin on Fri Dec 15 17:23:57 UTC 2023 , Edited by admin on Fri Dec 15 17:23:57 UTC 2023
|
PRIMARY | |||
|
145195-63-7
Created by
admin on Fri Dec 15 17:23:57 UTC 2023 , Edited by admin on Fri Dec 15 17:23:57 UTC 2023
|
PRIMARY |
Related Record | Type | Details | ||
---|---|---|---|---|
|
PARENT -> METABOLITE |
Active in vitro,but contribution should be little due to low plasma level
PLASMA
|
Related Record | Type | Details | ||
---|---|---|---|---|
|
PARENT -> IMPURITY |
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
|