Tìm theo
Tolcapone
Các tên gọi khác (8 ) :
  • (3,4-dihydroxy-5-nitrophenyl)(4-methylphenyl)methanone
  • 3,4-Dihydroxy-4'-methyl-5-nitrobenzophenone
  • 3,4-Dihydroxy-5-nitro-4'-methylbenzophenone
  • 4'-Methyl-3,4-dihydroxy-5-nitrobenzophenone
  • Tolcapon
  • Tolcapona
  • Tolcapone
  • Tolcaponum
Thuốc chống Parkinson
Thuốc Gốc
Small Molecule
CAS: 134308-13-7
ATC: N04BX01
ĐG : Legacy Pharmaceuticals Packaging LLC , http://www.legacypackaging.com
CTHH: C14H11NO5
PTK: 273.2408
Tolcapone is a drug that inhibits the enzyme catechol-O-methyl transferase (COMT). It is used in the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa medication. It is a yellow, odorless, non-hygroscopic, crystalline compound. Tolcapone is associated with a risk of hepatotoxicity. [Wikipedia]
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C14H11NO5
Phân tử khối
273.2408
Monoisotopic mass
273.063722467
InChI
InChI=1S/C14H11NO5/c1-8-2-4-9(5-3-8)13(17)10-6-11(15(19)20)14(18)12(16)7-10/h2-7,16,18H,1H3
InChI Key
InChIKey=MIQPIUSUKVNLNT-UHFFFAOYSA-N
IUPAC Name
5-[(4-methylphenyl)carbonyl]-3-nitrobenzene-1,2-diol
Traditional IUPAC Name
tolcapone
SMILES
CC1=CC=C(C=C1)C(=O)C1=CC(=C(O)C(O)=C1)[N+]([O-])=O
Độ hòa tan
5.69e-02 g/l
logP
4
logS
-3.7
pKa (strongest acidic)
5.17
pKa (Strongest Basic)
-6.4
PSA
103.35 Å2
Refractivity
72.96 m3·mol-1
Polarizability
26.44 Å3
Rotatable Bond Count
3
H Bond Acceptor Count
5
H Bond Donor Count
2
Physiological Charge
-1
Number of Rings
2
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Tolcapone is a potent, selective, and reversible inhibitor of catechol-O-methyltransferase (COMT). In humans, COMT is distributed throughout various organs. 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, 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 it to 3-methoxy-4-hydroxy-L-phenylalanine (3-OMD) in the brain and periphery. When tolcapone is given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor, such as carbidopa, plasma levels of levodopa are more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. It is believed that these sustained plasma levels of levodopa result in more constant dopaminergic stimulation in the brain, leading to greater effects on the signs and symptoms of Parkinson's disease in patients as well as increased levodopa adverse effects, sometimes requiring a decrease in the dose of levodopa.
Cơ Chế Tác Dụng : Tolcapone is a drug that inhibits the enzyme catechol-O-methyl transferase (COMT). It is used in the treatment of Parkinson's disease as an adjunct to levodopa/carbidopa medication. It is a yellow, odorless, non-hygroscopic, crystalline compound. Tolcapone is associated with a risk of hepatotoxicity. [Wikipedia] The precise mechanism of action of tolcapone is unknown, but it is believed to be related to its ability to inhibit COMT and alter the plasma pharmacokinetics of levodopa, resulting in an increase in plasma levodopa concentrations. The inhibition of COMT also causes a reduction in circulating 3-OMD as a result of decreased peripheral metabolism of levodopa. This may lead to an increase distribution of levodopa into the CNS through the reduction of its competitive substrate, 3-OMD, for transport mechanisms. Sustained levodopa concentrations presumably result in more consistent dopaminergic stimulation, resulting in greater reduction in the manifestations of parkinsonian syndrome.
Dược Động Học :
▧ Absorption :
Rapidly absorbed (absolute bioavailability is about 65%)
▧ Volume of Distribution :
* 9 L
▧ Protein binding :
> 99.9% (to serum albumin)
▧ Metabolism :
The main metabolic pathway of tolcapone is glucuronidation
▧ Route of Elimination :
Tolcapone is almost completely metabolized prior to excretion, with only a very small amount (0.5% of dose) found unchanged in urine. The glucuronide conjugate of tolcapone is mainly excreted in the urine but is also excreted in the bile.
▧ Half Life :
2-3.5 hours
▧ Clearance :
* 7 L/h
Độc Tính : LD50 = 1600 mg/kg (Orally in rats)
Chỉ Định : Used as an adjunct to levodopa/carbidopa therapy for the symptomatic treatment of Parkinson's Disease. This drug is generally reserved for patients with parkinsonian syndrome receiving levodopa/carbidopa who are experiencing symptom fluctuations and are not responding adequately to or are not candidates for other adjunctive therapies.
Tương Tác Thuốc :
  • Furazolidone Tolcapone and Furazolidone decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.
  • Isocarboxazid Tolcapone and Isocarboxazid decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.
  • Linezolid Tolcapone and Linezolid decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.
  • Moclobemide Tolcapone and Moclobemide decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.
  • Phenelzine Tolcapone and Phenelzine decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.
  • Procarbazine Tolcapone and Procarbazine decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.
  • Rasagiline Tolcapone and Rasagiline decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.
  • Selegiline Tolcapone and Selegiline decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.
  • Tranylcypromine Tolcapone and Tranylcypromine decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.
  • Triprolidine The CNS depressants, Triprolidine and Tolcapone, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
Liều Lượng & Cách Dùng : Tablet, film coated - Oral
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Tasmar 200 mg tablet
    Giá bán buôn : USD >7.44
    Đơn vị tính : tablet
  • Biệt dược thương mại : Tasmar 100 mg tablet
    Giá bán buôn : USD >8.13
    Đơn vị tính : tablet
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00323
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=4659569
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504932
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07949
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00786
ChemSpider
http://www.chemspider.com/Chemical-Structure.3848682.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50108877
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0187-0938-01
PharmGKB
http://www.pharmgkb.org/drug/PA451720
Wikipedia
http://en.wikipedia.org/wiki/Tolcapone
RxList
http://www.rxlist.com/cgi/generic3/tolcapone.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/tas1426.shtml
Drugs.com
http://www.drugs.com/cdi/tolcapone.html
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