Entacapone

Entacapone
Clinical data
Pronunciation	/ˌɛntəkəˈpoʊn/ or /ɛnˈtækəpoʊn/
Trade names	Comtan (single ingredient), Stalevo (multi-ingredient)
AHFS/Drugs.com	Monograph
MedlinePlus	a601236
License data	EU EMA: by INN; US DailyMed: Entacapone;
Pregnancy; category	AU: B3; ;
Routes of; administration	By mouth
ATC code	N04BX02 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only); BR: Class C1 (Other controlled substances); CA: ℞-only; UK: POM (Prescription only); US: ℞-only; EU: Rx-only;
Pharmacokinetic data
Bioavailability	35%
Protein binding	98% (binds to serum albumin)
Metabolism	Hepatic
Elimination half-life	0.4–0.7 hours
Excretion	Feces (90%), urine (10%)
Identifiers
	IUPAC name (2E)-2-Cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide;
CAS Number	130929-57-6 ;
PubChem CID	5281081;
IUPHAR/BPS	6647;
DrugBank	DB00494 ;
ChemSpider	4444537 ;
UNII	4975G9NM6T;
KEGG	D00781 ;
ChEBI	CHEBI:4798 ;
ChEMBL	ChEMBL953 ;
CompTox Dashboard (EPA)	DTXSID5046439 ;
ECHA InfoCard	100.128.566
Chemical and physical data
Formula	C14H15N3O5
Molar mass	305.290 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES [O-][N+](=O)c1cc(\C=C(/C#N)C(=O)N(CC)CC)cc(O)c1O;
	InChI 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+ ; Key:JRURYQJSLYLRLN-BJMVGYQFSA-N ;
	(verify)

Entacapone, sold under the brand name Comtan among others, is a medication commonly used in combination with other medications for the treatment of Parkinson's disease.^[2] Entacapone together with levodopa and carbidopa allows levodopa to have a longer effect in the brain and reduces Parkinson's disease signs and symptoms for a greater length of time than levodopa and carbidopa therapy alone.^[2]

Entacapone is a selective and reversible inhibitor of the enzyme catechol-O-methyltransferase (COMT).^[2] When taken together with levodopa (L-DOPA) and carbidopa, entacapone stops COMT from breaking down levodopa, resulting in an overall increase of levodopa remaining in the brain and body.^[2] Entacapone does not cross into the brain and hence does not inhibit COMT there.^[3]

Carbidopa/levodopa/entacapone (Stalevo), a medication developed by Orion Pharma and marketed by Novartis, is a single tablet formulation that contains levodopa, carbidopa, and entacapone.^[4]

^ Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.
^ ^a ^b ^c ^d "Comtan Full Prescribing Information-Novartis" (PDF). Pharma.us.novartis.com. July 2014. Archived from the original (PDF) on 15 March 2016. Retrieved 4 November 2015.
^ Habet S (August 2022). "Clinical Pharmacology of Entacapone (Comtan) From the FDA Reviewer". Int J Neuropsychopharmacol. 25 (7): 567–575. doi:10.1093/ijnp/pyac021. PMC 9352175. PMID 35302623. Entacapone is a potent and specific peripheral catechol-O-methyltransferase inhibitor. [...] Entacapone has no antiparkinsonian activity as a sole agent. Therefore, it must be given as an adjunct to LD and a peripherally acting DDC inhibitor, such as carbidopa. Entacapone acts peripherally and does not penetrate the blood-brain barrier (BBB). [...] It is poorly lipophilic and does not penetrate the BBB to any significant extent. Its clinical effects are thus due to peripheral COMT inhibition only (Nutt, 1998; Fahn et al, 2004). [...] Entacapone is poorly lipophilic. Therefore, its clinical effects are due to peripheral COMT inhibition alone. [...] Entacapone is a potent, specific, and reversible COMT inhibitor. The drug has been shown to act peripherally, but not centrally, when given at clinically effective doses.
^ "Stalevo- carbidopa, levodopa, and entacapone tablet, film coated". DailyMed. 7 January 2020. Retrieved 14 March 2020.

[1] Anvisa (31 March 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 4 April 2023). Archived from the original on 3 August 2023. Retrieved 16 August 2023.

[:02-2] "Comtan Full Prescribing Information-Novartis" (PDF). Pharma.us.novartis.com. July 2014. Archived from the original (PDF) on 15 March 2016. Retrieved 4 November 2015.

[Habet2022-3] Habet S (August 2022). "Clinical Pharmacology of Entacapone (Comtan) From the FDA Reviewer". Int J Neuropsychopharmacol. 25 (7): 567–575. doi:10.1093/ijnp/pyac021. PMC 9352175. PMID 35302623. Entacapone is a potent and specific peripheral catechol-O-methyltransferase inhibitor. [...] Entacapone has no antiparkinsonian activity as a sole agent. Therefore, it must be given as an adjunct to LD and a peripherally acting DDC inhibitor, such as carbidopa. Entacapone acts peripherally and does not penetrate the blood-brain barrier (BBB). [...] It is poorly lipophilic and does not penetrate the BBB to any significant extent. Its clinical effects are thus due to peripheral COMT inhibition only (Nutt, 1998; Fahn et al, 2004). [...] Entacapone is poorly lipophilic. Therefore, its clinical effects are due to peripheral COMT inhibition alone. [...] Entacapone is a potent, specific, and reversible COMT inhibitor. The drug has been shown to act peripherally, but not centrally, when given at clinically effective doses.

[4] "Stalevo- carbidopa, levodopa, and entacapone tablet, film coated". DailyMed. 7 January 2020. Retrieved 14 March 2020.

[1]

[2]

[3]

[4]