Entacapone

Structural formula
General
Non-proprietary name	Entacapone
other names	( E ) -2-cyano-3- (3,4-dihydroxy-5-nitro-phenyl) - N , N diethyl-prop-2-enamide
Molecular formula	C 14 H 15 N 3 O 5
External identifiers / databases
EC number	603-449-6
ECHA InfoCard	100.128.566
PubChem	5281081
ChemSpider	4444537
DrugBank	DB00494
Wikidata	Q416444
Drug information
ATC code	N04 BX02
Drug class	COMT inhibitors
properties
Molar mass	305.29 g mol −1
Physical state	firmly
Melting point	162-163 ° C
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances Caution
H and P phrases	H: 315-319-332-413
	P: ?
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Entacapone (manufacturer Novartis ) is a drug used to treat Parkinson's disease . The active ingredient belongs to the class of catecholamine - O -methyltransferase inhibitors, the so-called COMT inhibitors .

field of use

The drug is used to treat Parkinson's patients who develop motor fluctuations under L- DOPA therapy. It prevents the degradation of the dopamine precursor L -DOPA by COMT ( catechol- O- methyltransferase ) into ineffective metabolites and is taken at the same time with every L -DOPA dose. The effectiveness of the drug in treating fluctuations has been proven by studies. A prevention or delay in the occurrence of effect fluctuations by treating patients with a stable L- DOPA response with COMT inhibitors has so far only been proven in animal experiments. According to the German Society for Neurology, studies on humans are currently being carried out.

Contraindications are hepatic insufficiency and pheochromocytoma . Simultaneous administration of entacapone with non-selective monoamine oxidase inhibitors (MAO-A and MAO-B such as phenelzine, tranylcypromine) is contraindicated. The simultaneous administration of a selective MAO-A and a selective MAO-B inhibitor together with entacapone is also contraindicated.

Summary:

Administration: oral
Plasma half-life: 0.4-0.7 hours
Elimination: approx. 90% faecal, 10% renal

Extraction and presentation

Entacapone is produced by a Knoevenagel condensation of 3,4-dihydroxy-5-nitrobenzaldehyde with 2-cyano- N , N- diethylacetamide. In this synthesis variant, the ( E ) and ( Z ) isomers are formed in a ratio of 2: 1.

The isomers can be separated by crystallization of the hydrochloride salts.

Trade names

Monopreparations

Comtan (A, CH), Comtess (D, A)

Combination preparations

Stalevo (D, A, CH) (combination with L-Dopa and Carbidopa )

Web links

Public Assessment Report (EPAR) of the European Medicines Agency (EMA) for: Entacapone

Individual evidence

↑ U.S. Patent No. 5,135,950.
↑ Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of (2E) -2-cyano-3- (3,4-dihydroxy-5-nitrophenyl) -N, N-diethyl-2-propenamide in the Classification and Labeling Inventory of the European Chemicals Agency is reproduced from a self-classification by the distributor (ECHA), accessed on January 21, 2020.
↑ P. Novak, A. Kisic, T. Hrenar, T. Jednacak, S. Miljanic, G. Verbanec: In-line reaction monitoring of entacapone synthesis by Raman spectroscopy and multivariate analysis In: J Pharm Biomed Anal . 54 (2011) 660-666, doi : 10.1016 / j.jpba.2010.10.012 .

[1] U.S. Patent No. 5,135,950.

[2] Template: CL Inventory / not harmonized There is not yet a harmonized classification for this substance . A labeling of (2E) -2-cyano-3- (3,4-dihydroxy-5-nitrophenyl) -N, N-diethyl-2-propenamide in the Classification and Labeling Inventory of the European Chemicals Agency is reproduced from a self-classification by the distributor (ECHA), accessed on January 21, 2020.

[3] P. Novak, A. Kisic, T. Hrenar, T. Jednacak, S. Miljanic, G. Verbanec: In-line reaction monitoring of entacapone synthesis by Raman spectroscopy and multivariate analysis In: J Pharm Biomed Anal . 54 (2011) 660-666, doi : 10.1016 / j.jpba.2010.10.012 .