Entacapone
Synonym(s):2-Cyano-N,N-diethyl-3-(3,4-dihydroxy-5-nitrophenyl)propenamide
- CAS NO.:130929-57-6
- Empirical Formula: C14H15N3O5
- Molecular Weight: 305.29
- MDL number: MFCD00866580
- EINECS: 212-686-0
- SAFETY DATA SHEET (SDS)
- Update Date: 2024-10-25 16:21:11
What is Entacapone?
Absorption
Entacapone is rapidly absorbed (approximately 1 hour). The absolute bioavailability following oral administration is 35%.
Toxicity
Side effect include increase the occurrence of orthostatic hypotension, severe rhabdomyolysis, dyskinesia, hallucinations, hyperkinesia, hypokinesia, dizziness, fatigu,e gastrointestinal effects including abdominal pain constipation diarrhea nausea
Description
Entacapone was introduced in Finland, Germany and Sweden as an adjunctive treatment with L-dopa in Parkinson’s disease. Entacapone is the second drug in its class to reach the market; it can be obtained by basecatalyzed condensation of the corresponding benzaldehyde with a cyanoacetamide. Entacapone is a highly selective and orally-active catechol-0- methyltransferase (COMT) inhibitor ; by inhibiting metabolism of L-dopa when given as an adjuvant in patients with Parkinson’s disease, Entacapone markedly prolongs the effects of L-dopa and improves its bioavailability. Results from clinical studies showed that 200mglday Entacapone coadministered with L-dopa lowered the dose of the latter required to reduce fluctuations in motor performance.
Chemical properties
Yellow Crystalline Solid
Originator
Orion Pharma (Finland)
The Uses of Entacapone
antiparkinsinian;catechol-O-methyl transferase inhibitor
The Uses of Entacapone
This compound belongs to the cinnamic acid amides. These are amides of cinnamic acids. 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-
The Uses of Entacapone
(E)-Isomer of Entacapone polymorphic form A. Peripherally acting inhibitor of catechol-O-methyl transferase (COMT), an enzyme involved in the metabolism of catecholamine neurotransmitters and related drugs. Antiparkinsonian
Background
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.
Definition
ChEBI: A monocarboxylic acid amide that is N,N-diethylprop-2-enamide in which the hydrogen at position 2 is substituted by a cyano group and the hydrogen at the 3E position is substituted by a 3,4-dihydroxy-5 nitrophenyl group.
Indications
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".
What are the applications of Application
Entacapone is a peripherally acting inhibitor of catechol-O-methyl transferase
Manufacturing Process
N,N-Diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)acrylamide (2-
Propenamide, 2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl).
A solution containing 1.83 g of 3,4-dihydroxy-5-nitrobenzaldehyde, 1.5 g of
N,N-diethylcyanoacetamide and catalytic amount of piperidine acetate in 40
ml of dry ethanol was refluxed over night. After cooling the solvent was
evaporated in vacuo and the residue was recrystallized from waterdimethylformamide. Yield of desired product was 2.23 g (73%), melting point
153°-156°C.
brand name
Comtan(Orion);Comtess.
Therapeutic Function
Antiparkinsonian
General Description
Entacapone, (E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethyl-2-propenamide (Comtan),is a nitrocatechol that is practically insoluble in water (pKa=4.50). Entacapone is rapidly absorbed after oral administrationand does not cross the BBB. Entacapone does not distributewidely into tissues because of its high plasma proteinbinding and it is completely metabolized before excretion.The main metabolic pathway is by isomerization to the cisisomerfollowed by direct glucuronidation of the parent andthe cis-isomer. The glucuronide conjugates are inactive.Entacapone is eliminated in the feces (90%) and urine (10%).Entacapone is indicated as an adjunct to levodopa/carbidopato treat patients with idiopathic PD who experience the signsand symptoms of end-of-dose wearing off.
Biochem/physiol Actions
Entacapone is a catechol-O-methyl transferase (COMT) inhibitor. Used in treatment of Parkinson′s disease, entacapone is administered with L-DOPA to inihibit COMT from converting L-DOPA into a compound that cannot cross the blood brain barrier.
Pharmacokinetics
Entacapone is structurally and pharmacologically related to tolcapone, but unlike tolcapone, is not associated with hepatotoxicity. Entacapone is used in the treatment of Parkinson’s disease as an adjunct to levodopa/carbidopa therapy. Entacapone selectively and reversiblly inhibits catechol-O-methyltransferase (COMT). In mammals, COMT is distributed throughout various organs with the highest activities in the liver and kidney. COMT also occurs in the heart, lung, smooth and skeletal muscles, intestinal tract, reproductive organs, various glands, adipose tissue, skin, blood cells and neuronal tissues, especially in glial cells. COMT catalyzes the transfer of the methyl group of S-adenosyl-L-methionine to the phenolic group of substrates that contain a catechol structure. Physiological substrates of COMT include dopa, catecholamines (dopamine, norepinephrine, and epinephrine) and their hydroxylated metabolites. The function of COMT is the elimination of biologically active catechols and some other hydroxylated metabolites. COMT is responsible for the elimination of biologically active catechols and some other hydroxylated metabolites. In the presence of a decarboxylase inhibitor, COMT becomes the major metabolizing enzyme for levodopa, catalyzing the it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery.
Drug interactions
Potentially hazardous interactions with other drugs Anticoagulants: enhances anticoagulant effect of warfarinAntidepressants: use with caution in combination with moclobemide, tricyclics and venlafaxine; avoid with MAOIs. Dopaminergics: possibly enhances effects of apomorphine; possibly reduces concentration of rasagiline; max dose of selegiline is 10 mg in combination.
Metabolism
Entacapone undergoes extensive first-pass metabolism to form glucuronide metabolites.It is eliminated mainly in the faeces with about 10-20% being excreted in the urine, mainly as glucuronide conjugates
Metabolism
Metabolized via isomerization to the cis-isomer, followed by direct glucuronidation of the parent and cis-isomer.
storage
Store at RT
References
1) Forsberg?et al.?(2003),?Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat; J. Pharmacol. Exp. Ther.,?304?498 2) Merello?et al. (1994),?Effect of entacapone, a peripherally acting catechol-O-methyltransferase inhibitor, on the motor response to acute treatment with levodopa in patients with Parkinson’s disease; J. Neurol. Neurosurg. Psychiatry,?57?186 3) Giovanni?et al. (2010),?Entacapone and tolcapone, two catechol O-methyltransferase inhibitors, block fibril formation of alpha-synuclein and beta amyloid and protect against amyloid-induced toxicity; J. Biol. Chem.,?285?14941 4) Chen?et al. (2016),?Entacapone is an Antioxident More Potent than Vitamin C and Vitamin E for Scavenging of Hypochlorous Acid and Peroxynitrite, and the Inhibition of Oxidative Stress-induced Cell Death; Med. Sci. Monit.,?22?687
Properties of Entacapone
Melting point: | 162-1630C |
Boiling point: | 526.6±50.0 °C(Predicted) |
Density | 1.392±0.06 g/cm3(Predicted) |
storage temp. | 2-8°C |
solubility | DMSO: soluble20mg/mL, clear |
pka | pKa ~4.5(at 25℃) |
form | powder |
color | white to light brown |
Stability: | Stable for 1 year from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20°C for up to 1 month. |
CAS DataBase Reference | 130929-57-6(CAS DataBase Reference) |
Safety information for Entacapone
Signal word | Warning |
Pictogram(s) |
Exclamation Mark Irritant GHS07 |
GHS Hazard Statements |
H315:Skin corrosion/irritation H319:Serious eye damage/eye irritation |
Precautionary Statement Codes |
P264:Wash hands thoroughly after handling. P264:Wash skin thouroughly after handling. P280:Wear protective gloves/protective clothing/eye protection/face protection. P302+P352:IF ON SKIN: wash with plenty of soap and water. P305+P351+P338:IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing. P332+P313:IF SKIN irritation occurs: Get medical advice/attention. P337+P313:IF eye irritation persists: Get medical advice/attention. |
Computed Descriptors for Entacapone
InChIKey | JRURYQJSLYLRLN-BJMVGYQFSA-N |
Abamectin manufacturer
Ramdev Chemicals Pvt Ltd
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