Tìm theo
Entacapone
Các tên gọi khác (7 ) :
  • (e)-alpha-Cyano-N,N-diethyl-3,4-dihydroxy-5-nitrocinnamamide
  • Comtan
  • Comtess
  • Entacapona
  • Entacapone
  • Entacaponum
  • N,N-Diethyl-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl) acrylamide
enzyme inhibitors, antiparkinson agents, antidyskinetics
Thuốc Gốc
Small Molecule
CAS: 130929-57-6
ATC: N04BX02
ĐG : Cardinal Health , http://www.cardinal.com
CTHH: C14H15N3O5
PTK: 305.286
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C14H15N3O5
Phân tử khối
305.286
Monoisotopic mass
305.101170605
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+
InChI Key
InChIKey=JRURYQJSLYLRLN-BJMVGYQFSA-N
IUPAC Name
(2E)-2-cyano-3-(3,4-dihydroxy-5-nitrophenyl)-N,N-diethylprop-2-enamide
Traditional IUPAC Name
entacapone
SMILES
CCN(CC)C(=O)C(=C\C1=CC(=C(O)C(O)=C1)[N+]([O-])=O)\C#N
Độ hòa tan
7.97e-02 g/l
logP
2.8
logS
-3.6
pKa (strongest acidic)
5.68
pKa (Strongest Basic)
-0.036
PSA
130.38 Å2
Refractivity
80.51 m3·mol-1
Polarizability
29.48 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
6
H Bond Donor Count
2
Physiological Charge
-1
Number of Rings
1
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : 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.
Cơ Chế Tác Dụng : 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.
Dược Động Học :
▧ 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
Độc Tính : 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
Chỉ Định : 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".
Tương Tác Thuốc :
  • 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
  • Isoetarine Entacapone increases the effect and toxicity of the sympathomimetic, isoetharine.
  • Isoprenaline 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.
Liều Lượng & Cách Dùng : Tablet - Oral
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Comtan 200 mg tablet
    Giá bán buôn : USD >2.96
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty : Root
    Sản phẩm biệt dược : Anxopone
  • Công ty : Novartis
    Sản phẩm biệt dược : Comtade
  • Công ty : Orion
    Sản phẩm biệt dược : Comtan
  • Công ty : Orion
    Sản phẩm biệt dược : Comtess
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00494
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5281081
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46508734
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07943
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00781
ChemSpider
http://www.chemspider.com/Chemical-Structure.4444537.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0078-0327-05
PharmGKB
http://www.pharmgkb.org/drug/PA164748726
Wikipedia
http://en.wikipedia.org/wiki/Entacapone
RxList
http://www.rxlist.com/cgi/generic3/entac.htm
Drugs.com
http://www.drugs.com/cdi/entacapone.html
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