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药品详细

Entacapone (恩他卡朋 )

化学结构式图
中文名
恩他卡朋
英文名
Entacapone
分子式
Not Available
化学名
(2E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide
分子量
Average: 305.286
Monoisotopic: 305.101170605
CAS号
130929-57-6
ATC分类
N04B 未知
药物类型
small molecule
阶段
商品名
Comtan;Comtess;
同义名
Entacapona [INN-Spanish];entacapone;Entacapone [Usan:Inn];Entacaponum [INN-Latin];
基本介绍

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.

生产厂家
  • Orion corp
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Najib J: Entacapone: a catechol-O-methyltransferase inhibitor for the adjunctive treatment of Parkinson’s disease. Clin Ther. 2001 Jun;23(6):802-32; discussion 771. Pubmed
  2. Chong BS, Mersfelder TL: Entacapone. Ann Pharmacother. 2000 Sep;34(9):1056-65. Pubmed
  3. Poewe WH, Deuschl G, Gordin A, Kultalahti ER, Leinonen M: 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). Acta Neurol Scand. 2002 Apr;105(4):245-55. Pubmed
  4. Brooks DJ, Sagar H: Entacapone is beneficial in both fluctuating and non-fluctuating patients with Parkinson’s disease: a randomised, placebo controlled, double blind, six month study. J Neurol Neurosurg Psychiatry. 2003 Aug;74(8):1071-9. Pubmed
  5. Forsberg M, Lehtonen M, Heikkinen M, Savolainen J, Jarvinen T, Mannisto PT: Pharmacokinetics and pharmacodynamics of entacapone and tolcapone after acute and repeated administration: a comparative study in the rat. J Pharmacol Exp Ther. 2003 Feb;304(2):498-506. Pubmed
  6. Kaakkola S: Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson’s disease. Drugs. 2000 Jun;59(6):1233-50. Pubmed
剂型
Form Route Strength
Tablet Oral
规格
Unit description Cost Unit
Comtan 200 mg tablet 2.96 USD tablet
化合物类型
Type small molecule
Classes
  • Phenols and Derivatives
  • Nitrobenzenes
  • Phenylpropenes
  • Nitrophenols and Derivatives
  • Aminophenols and Derivatives
  • Cinnamaldehydes
Substructures
  • Hydroxy Compounds
  • Phenols and Derivatives
  • Alkanes and Alkenes
  • Nitrobenzenes
  • Oxoazaniums
  • Amino Ketones
  • Phenylpropenes
  • Nitriles and Derivatives
  • Nitrophenols and Derivatives
  • Benzene and Derivatives
  • Aliphatic and Aryl Amines
  • Aminophenols and Derivatives
  • Nitro compounds
  • Cyanides
  • Catechols
  • Aromatic compounds
  • Cinnamaldehydes
  • Carboxamides and Derivatives
  • Styrene Derivatives
  • Phenyl Esters
  • Anilines
适应症
PARKINSON 帕金森氏症;
药理
Indication 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".
Pharmacodynamics 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 is a selective and reversible inhibitor of 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.
Mechanism of action 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.
Absorption Entacapone is rapidly absorbed (approximately 1 hour). The absolute bioavailability following oral administration is 35%.
Volume of distribution
  • 20 L
Protein binding 98% (bind to serum albumin)
Metabolism

Metabolized via isomerization to the cis-isomer, followed by direct glucuronidation of the parent and cis-isomer.
Route of elimination Entacapone is almost completely metabolized prior to excretion, with only a very small amount (0.2% of dose) found unchanged in urine. As only about 10% of the entacapone dose is excreted in urine as parent compound and conjugated glucuronide, biliary excretion appears to be the major route of excretion of this drug.
Half life 0.4-0.7 hour
Clearance
  • 850 mL/min
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
Affected organisms
  • Humans and other mammals
Pathways Not Available
理化性质
Properties
State solid
Melting point Not Available
Experimental Properties
Property Value Source
logP 2.8 PhysProp
Predicted Properties
Property Value Source
water solubility 7.97e-02 g/l ALOGPS
logP 2.50 ALOGPS
logP 1.63 ChemAxon Molconvert
logS -3.58 ALOGPS
pKa 10.72 ChemAxon Molconvert
hydrogen acceptor count 6 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 130.38 ChemAxon Molconvert
rotatable bond count 5 ChemAxon Molconvert
refractivity 80.51 ChemAxon Molconvert
polarizability 29.48 ChemAxon Molconvert
药物相互作用
Drug Interaction
Apomorphine Entacapone increases the effect and toxicity of the sympathomimetic, apomorphine.
Bitolterol Entacapone may increase the effect and toxicity of bitolterol.
Dobutamine Entacapone increases the effect and toxicity of the sympathomimetic, dobutamine.
Dopamine Entacapone increases the effect and toxicity of the sympathomimetic, dopamine.
Epinephrine Entacapone may increase the effect and toxicity of the sympathomimetic, epinephrine.
Isocarboxazid Possible hypertensive crisis with this combination
Isoetharine Entacapone increases the effect and toxicity of the sympathomimetic, isoetharine.
Isoproterenol Entacapone increases the effect and toxicity of the sympathomimetic, isoproterenol.
Methyldopa Entacapone may increase the effect and toxicity of the sympathomimetic, methyldopa.
Norepinephrine Entacapone increases the effect and toxicity of the sympathomimetic, norepinephrine.
Phenelzine Possible hypertensive crisis with this combination
Tranylcypromine Additive inhibition of endogenous catecholamine metabolism may increase the therapeutic/adverse effects of both agents. Concomitant therapy should be avoided.
Triprolidine The CNS depressants, Triprolidine and Entacapone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
食物相互作用
  • Take without regard to meals.

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