Identification

Name
Tolcapone
Accession Number
DB00323  (APRD00445)
Type
Small Molecule
Groups
Approved, Withdrawn
Description

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]

Structure
Thumb
Synonyms
  • (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
External IDs
Ro 40-7592
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TasmarTablet100 mgOralHoffmann La Roche1997-10-201999-01-11Canada
TasmarTablet, film coated100 mgOralMeda Ab1997-08-27Not applicableEu
TasmarTablet, film coated200 mgOralMeda Ab1997-08-27Not applicableEu
TasmarTablet, film coated100 mgOralMeda Ab1997-08-27Not applicableEu
TasmarTablet, film coated100 mgOralMeda Ab1997-08-27Not applicableEu
TasmarTablet, film coated200 mgOralMeda Ab1997-08-27Not applicableEu
TasmarTablet, film coated100 mgOralMeda Ab1997-08-27Not applicableEu
TasmarTablet, film coated100 mg/1OralValeant Pharmaceuticals North America2004-07-27Not applicableUs
TasmarTablet200 mgOralHoffmann La Roche1997-10-201999-01-11Canada
TasmarTablet, film coated100 mgOralMeda Ab1997-08-27Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
TolcaponeTablet, coated100 mg/1OralPar Pharmaceutical2015-01-06Not applicableUs
International/Other Brands
Sen De Ning (Dexin Runsheng Pharmaceutical)
Categories
UNII
CIF6334OLY
CAS number
134308-13-7
Weight
Average: 273.2408
Monoisotopic: 273.063722467
Chemical Formula
C14H11NO5
InChI Key
MIQPIUSUKVNLNT-UHFFFAOYSA-N
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
IUPAC Name
5-(4-methylbenzoyl)-3-nitrobenzene-1,2-diol
SMILES
CC1=CC=C(C=C1)C(=O)C1=CC(=C(O)C(O)=C1)[N+]([O-])=O

Pharmacology

Indication

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.

Structured Indications
Pharmacodynamics

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.

Mechanism of action

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.

TargetActionsOrganism
ACatechol O-methyltransferase
inhibitor
Human
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
Toxicity

LD50 = 1600 mg/kg (Orally in rats)

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Tolcapone is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.Experimental
AmifostineThe risk or severity of adverse effects can be increased when Amifostine is combined with Tolcapone.Approved, Investigational
AmiodaroneThe risk or severity of adverse effects can be increased when Amiodarone is combined with Tolcapone.Approved, Investigational
AmobarbitalAmobarbital may increase the hypotensive activities of Tolcapone.Approved, Illicit
AmphetamineThe risk or severity of adverse effects can be increased when Tolcapone is combined with Amphetamine.Approved, Illicit
Amphotericin BThe risk or severity of adverse effects can be increased when Amphotericin B is combined with Tolcapone.Approved, Investigational
ApomorphineThe risk or severity of adverse effects can be increased when Apomorphine is combined with Tolcapone.Approved, Investigational
AripiprazoleAripiprazole may increase the hypotensive activities of Tolcapone.Approved, Investigational
ArotinololThe risk or severity of adverse effects can be increased when Arotinolol is combined with Tolcapone.Investigational
Arsenic trioxideThe risk or severity of adverse effects can be increased when Arsenic trioxide is combined with Tolcapone.Approved, Investigational
BarbexacloneBarbexaclone may increase the hypotensive activities of Tolcapone.Experimental
BarbitalBarbital may increase the hypotensive activities of Tolcapone.Illicit
BarnidipineThe risk or severity of adverse effects can be increased when Barnidipine is combined with Tolcapone.Approved
BepridilThe risk or severity of adverse effects can be increased when Bepridil is combined with Tolcapone.Approved, Withdrawn
BortezomibThe risk or severity of adverse effects can be increased when Bortezomib is combined with Tolcapone.Approved, Investigational
BrofaromineThe risk or severity of adverse effects can be increased when Tolcapone is combined with Brofaromine.Experimental
BromocriptineThe risk or severity of adverse effects can be increased when Bromocriptine is combined with Tolcapone.Approved, Investigational
CarbetocinThe risk or severity of adverse effects can be increased when Carbetocin is combined with Tolcapone.Approved
CilnidipineThe risk or severity of adverse effects can be increased when Cilnidipine is combined with Tolcapone.Approved, Investigational
ClofarabineThe risk or severity of adverse effects can be increased when Clofarabine is combined with Tolcapone.Approved, Investigational
ConivaptanThe risk or severity of adverse effects can be increased when Conivaptan is combined with Tolcapone.Approved, Investigational
Conjugated estrogensThe metabolism of Conjugated estrogens can be decreased when combined with Tolcapone.Approved
DiethylstilbestrolThe metabolism of Diethylstilbestrol can be decreased when combined with Tolcapone.Approved, Investigational
DobutamineThe metabolism of Dobutamine can be decreased when combined with Tolcapone.Approved
DopamineThe metabolism of Dopamine can be decreased when combined with Tolcapone.Approved
DuloxetineTolcapone may increase the orthostatic hypotensive activities of Duloxetine.Approved
EfonidipineThe risk or severity of adverse effects can be increased when Efonidipine is combined with Tolcapone.Approved, Investigational
EnalaprilatThe risk or severity of adverse effects can be increased when Enalaprilat is combined with Tolcapone.Approved
EpoprostenolThe risk or severity of adverse effects can be increased when Epoprostenol is combined with Tolcapone.Approved
FenoldopamThe risk or severity of adverse effects can be increased when Fenoldopam is combined with Tolcapone.Approved
FimasartanThe risk or severity of adverse effects can be increased when Fimasartan is combined with Tolcapone.Approved, Investigational
FurazolidoneThe risk or severity of adverse effects can be increased when Tolcapone is combined with Furazolidone.Approved, Investigational, Vet Approved
HarmalineThe risk or severity of adverse effects can be increased when Tolcapone is combined with Harmaline.Experimental
HexobarbitalHexobarbital may increase the hypotensive activities of Tolcapone.Approved
HydroflumethiazideThe risk or severity of adverse effects can be increased when Hydroflumethiazide is combined with Tolcapone.Approved, Investigational
IloprostThe risk or severity of adverse effects can be increased when Iloprost is combined with Tolcapone.Approved, Investigational
ImidaprilThe risk or severity of adverse effects can be increased when Imidapril is combined with Tolcapone.Investigational
IndoraminThe risk or severity of adverse effects can be increased when Indoramin is combined with Tolcapone.Withdrawn
IproniazidThe risk or severity of adverse effects can be increased when Tolcapone is combined with Iproniazid.Withdrawn
IsocarboxazidThe risk or severity of adverse effects can be increased when Tolcapone is combined with Isocarboxazid.Approved
LacidipineTolcapone may increase the hypotensive activities of Lacidipine.Approved, Investigational
LercanidipineThe risk or severity of adverse effects can be increased when Lercanidipine is combined with Tolcapone.Approved, Investigational
LevodopaTolcapone may increase the orthostatic hypotensive activities of Levodopa.Approved
LevosimendanThe risk or severity of adverse effects can be increased when Levosimendan is combined with Tolcapone.Approved, Investigational
LofexidineThe risk or severity of adverse effects can be increased when Lofexidine is combined with Tolcapone.Approved, Investigational
MethohexitalMethohexital may increase the hypotensive activities of Tolcapone.Approved
MethyldopaThe metabolism of Methyldopa can be decreased when combined with Tolcapone.Approved
MethylphenobarbitalMethylphenobarbital may increase the hypotensive activities of Tolcapone.Approved
MicafunginThe metabolism of Micafungin can be decreased when combined with Tolcapone.Approved, Investigational
MinaprineThe risk or severity of adverse effects can be increased when Tolcapone is combined with Minaprine.Approved
MoclobemideThe risk or severity of adverse effects can be increased when Tolcapone is combined with Moclobemide.Approved
MoxonidineThe risk or severity of adverse effects can be increased when Moxonidine is combined with Tolcapone.Approved, Investigational
NabiloneThe risk or severity of adverse effects can be increased when Nabilone is combined with Tolcapone.Approved, Investigational
NialamideThe risk or severity of adverse effects can be increased when Tolcapone is combined with Nialamide.Withdrawn
NicorandilNicorandil may increase the hypotensive activities of Tolcapone.Approved, Investigational
NilvadipineThe risk or severity of adverse effects can be increased when Nilvadipine is combined with Tolcapone.Approved, Investigational
NitrendipineThe risk or severity of adverse effects can be increased when Nitrendipine is combined with Tolcapone.Approved, Investigational
Nitric OxideThe risk or severity of adverse effects can be increased when Nitric Oxide is combined with Tolcapone.Approved
ObinutuzumabThe risk or severity of adverse effects can be increased when Obinutuzumab is combined with Tolcapone.Approved
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Tolcapone.Approved, Vet Approved
PargylineThe risk or severity of adverse effects can be increased when Tolcapone is combined with Pargyline.Approved
PentobarbitalPentobarbital may increase the hypotensive activities of Tolcapone.Approved, Vet Approved
PhenelzineThe risk or severity of adverse effects can be increased when Tolcapone is combined with Phenelzine.Approved
PhenobarbitalPhenobarbital may increase the hypotensive activities of Tolcapone.Approved
PhenoxybenzamineThe risk or severity of adverse effects can be increased when Phenoxybenzamine is combined with Tolcapone.Approved
PhentolamineThe risk or severity of adverse effects can be increased when Phentolamine is combined with Tolcapone.Approved
PipamperoneThe therapeutic efficacy of Pipamperone can be decreased when used in combination with Tolcapone.Approved, Investigational
PirlindoleThe risk or severity of adverse effects can be increased when Tolcapone is combined with Pirlindole.Approved
PramipexoleThe risk or severity of adverse effects can be increased when Pramipexole is combined with Tolcapone.Approved, Investigational
PrimidonePrimidone may increase the hypotensive activities of Tolcapone.Approved, Vet Approved
ProcarbazineThe risk or severity of adverse effects can be increased when Tolcapone is combined with Procarbazine.Approved
RasagilineThe risk or severity of adverse effects can be increased when Tolcapone is combined with Rasagiline.Approved
RisperidoneTolcapone may increase the hypotensive activities of Risperidone.Approved, Investigational
RopiniroleThe risk or severity of adverse effects can be increased when Ropinirole is combined with Tolcapone.Approved, Investigational
RotigotineThe risk or severity of adverse effects can be increased when Rotigotine is combined with Tolcapone.Approved
SacubitrilThe risk or severity of adverse effects can be increased when Sacubitril is combined with Tolcapone.Approved
SecobarbitalSecobarbital may increase the hypotensive activities of Tolcapone.Approved, Vet Approved
SelegilineThe risk or severity of adverse effects can be increased when Tolcapone is combined with Selegiline.Approved, Investigational, Vet Approved
Sodium NitriteThe risk or severity of adverse effects can be increased when Sodium Nitrite is combined with Tolcapone.Approved
StreptokinaseThe risk or severity of adverse effects can be increased when Streptokinase is combined with Tolcapone.Approved, Investigational
TamsulosinThe risk or severity of adverse effects can be increased when Tamsulosin is combined with Tolcapone.Approved, Investigational
ThalidomideThe risk or severity of adverse effects can be increased when Thalidomide is combined with Tolcapone.Approved, Investigational, Withdrawn
ThiamylalThiamylal may increase the hypotensive activities of Tolcapone.Approved, Vet Approved
ThiopentalThiopental may increase the hypotensive activities of Tolcapone.Approved, Vet Approved
TolazolineThe risk or severity of adverse effects can be increased when Tolazoline is combined with Tolcapone.Approved, Vet Approved
ToloxatoneThe risk or severity of adverse effects can be increased when Tolcapone is combined with Toloxatone.Approved
Trans-2-PhenylcyclopropylamineThe risk or severity of adverse effects can be increased when Tolcapone is combined with Trans-2-Phenylcyclopropylamine.Experimental
TranylcypromineThe risk or severity of adverse effects can be increased when Tolcapone is combined with Tranylcypromine.Approved
TretinoinThe risk or severity of adverse effects can be increased when Tolcapone is combined with Tretinoin.Approved, Investigational, Nutraceutical
Food Interactions
Not Available

References

General References
  1. Guay DR: Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of Parkinson's disease. Pharmacotherapy. 1999 Jan;19(1):6-20. [PubMed:9917075]
  2. Keating GM, Lyseng-Williamson KA: Tolcapone: a review of its use in the management of Parkinson's disease. CNS Drugs. 2005;19(2):165-84. [PubMed:15697329]
  3. Truong DD: Tolcapone: review of its pharmacology and use as adjunctive therapy in patients with Parkinson's disease. Clin Interv Aging. 2009;4:109-13. Epub 2009 May 14. [PubMed:19503773]
  4. 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:12538800]
  5. Kaakkola S: Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. Drugs. 2000 Jun;59(6):1233-50. [PubMed:10882160]
External Links
Human Metabolome Database
HMDB14468
KEGG Drug
D00786
KEGG Compound
C07949
PubChem Compound
4659569
PubChem Substance
46504932
ChemSpider
3848682
BindingDB
50108877
ChEBI
63630
ChEMBL
CHEMBL1324
Therapeutic Targets Database
DAP000607
PharmGKB
PA451720
HET
TCW
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Tolcapone
ATC Codes
N04BX01 — Tolcapone
PDB Entries
3s68 / 4d7b / 4pyl / 5a6i
FDA label
Download (71.3 KB)
MSDS
Download (17.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedTreatmentHealthy Volunteers1
1RecruitingTreatmentMedulloblastomas / Neuroblastomas1
1Unknown StatusTreatmentCocaine-Related Disorders1
2Active Not RecruitingTreatmentFrontotemporal Lobar Degeneration1
2CompletedNot AvailableSchizophrenic Disorders1
2CompletedTreatmentNicotine Dependence1
2CompletedTreatmentPathological Gambling1
2CompletedTreatmentTobacco Use Disorders1
2Enrolling by InvitationTreatmentBrain Injuries,Traumatic / Brain Injury / Mild Cognitive Impairment (MCI) / Neurocognitive Disorders1
2RecruitingTreatmentAlcohol Use Disorder (AUD)1
2, 3Not Yet RecruitingTreatmentObsessive-Compulsive Disorder (OCD)1
4CompletedTreatmentParkinson's Disease (PD)1
Not AvailableActive Not RecruitingBasic ScienceAddictions1
Not AvailableActive Not RecruitingBasic ScienceImpulsive Behaviors1
Not AvailableCompletedBasic SciencePathological Gambling1
Not AvailableRecruitingNot AvailableAtypical Parkinson Disease / Corticobasal Degeneration / Gait, Frontal / Multiple System Atrophy (MSA) / Parkinson's Disease (PD) / Parkinsonian Disorders / Progressive Supranuclear Palsy (PSP)1
Not AvailableRecruitingBasic ScienceAlcohol Abuse / Impulsive Behaviors1
Not AvailableRecruitingBasic ScienceMild Traumatic Brain Injury (MTBI)1
Not AvailableRecruitingTreatmentNicotine Dependence1

Pharmacoeconomics

Manufacturers
  • Valeant pharmaceuticals international
Packagers
Dosage forms
FormRouteStrength
TabletOral100 mg
TabletOral200 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral200 mg
Tablet, coatedOral100 mg/1
Tablet, film coatedOral100 mg/1
Prices
Unit descriptionCostUnit
Tasmar 100 mg tablet8.13USD tablet
Tasmar 200 mg tablet7.44USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5476875No1992-12-192012-12-19Us
US5236952No1995-01-292012-01-29Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0569 mg/mLALOGPS
logP2.63ALOGPS
logP3.28ChemAxon
logS-3.7ALOGPS
pKa (Strongest Acidic)5.17ChemAxon
pKa (Strongest Basic)-6.4ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area103.35 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity72.96 m3·mol-1ChemAxon
Polarizability26.44 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9041
Blood Brain Barrier-0.9418
Caco-2 permeable-0.5422
P-glycoprotein substrateNon-substrate0.6612
P-glycoprotein inhibitor INon-inhibitor0.6371
P-glycoprotein inhibitor IINon-inhibitor0.9128
Renal organic cation transporterNon-inhibitor0.933
CYP450 2C9 substrateNon-substrate0.6554
CYP450 2D6 substrateNon-substrate0.894
CYP450 3A4 substrateSubstrate0.5245
CYP450 1A2 substrateNon-inhibitor0.9199
CYP450 2C9 inhibitorInhibitor0.8317
CYP450 2D6 inhibitorNon-inhibitor0.9135
CYP450 2C19 inhibitorNon-inhibitor0.8762
CYP450 3A4 inhibitorNon-inhibitor0.6585
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5984
Ames testNon AMES toxic0.9132
CarcinogenicityNon-carcinogens0.6079
BiodegradationNot ready biodegradable0.9433
Rat acute toxicity2.2574 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8346
hERG inhibition (predictor II)Non-inhibitor0.8311
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-00e9-0980000000-495401c19ad2c2091c1a

Taxonomy

Description
This compound belongs to the class of organic compounds known as benzophenones. These are organic compounds containing a ketone attached to two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Benzophenones
Direct Parent
Benzophenones
Alternative Parents
Aryl-phenylketones / Diphenylmethanes / Nitrophenols / Nitrobenzenes / Benzoyl derivatives / Catechols / Nitroaromatic compounds / Toluenes / 1-hydroxy-4-unsubstituted benzenoids / 1-hydroxy-2-unsubstituted benzenoids
show 6 more
Substituents
Benzophenone / Diphenylmethane / Aryl-phenylketone / Nitrophenol / Nitrobenzene / Nitroaromatic compound / Benzoyl / Catechol / Aryl ketone / 1-hydroxy-4-unsubstituted benzenoid
show 18 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
benzophenones (CHEBI:63630) / a small molecule (CPD-7664)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
O-methyltransferase activity
Specific Function
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOP...
Gene Name
COMT
Uniprot ID
P21964
Uniprot Name
Catechol O-methyltransferase
Molecular Weight
30036.77 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Ries V, Selzer R, Eichhorn T, Oertel WH, Eggert K: Replacing a dopamine agonist by the COMT-inhibitor tolcapone as an adjunct to L-dopa in the treatment of Parkinson's disease: a randomized, multicenter, open-label, parallel-group study. Clin Neuropharmacol. 2010 May;33(3):142-50. doi: 10.1097/WNF.0b013e3181d99d6f. [PubMed:20502133]
  3. Guay DR: Tolcapone, a selective catechol-O-methyltransferase inhibitor for treatment of Parkinson's disease. Pharmacotherapy. 1999 Jan;19(1):6-20. [PubMed:9917075]
  4. Keating GM, Lyseng-Williamson KA: Tolcapone: a review of its use in the management of Parkinson's disease. CNS Drugs. 2005;19(2):165-84. [PubMed:15697329]
  5. Truong DD: Tolcapone: review of its pharmacology and use as adjunctive therapy in patients with Parkinson's disease. Clin Interv Aging. 2009;4:109-13. Epub 2009 May 14. [PubMed:19503773]
  6. Apud JA, Mattay V, Chen J, Kolachana BS, Callicott JH, Rasetti R, Alce G, Iudicello JE, Akbar N, Egan MF, Goldberg TE, Weinberger DR: Tolcapone improves cognition and cortical information processing in normal human subjects. Neuropsychopharmacology. 2007 May;32(5):1011-20. Epub 2006 Oct 25. [PubMed:17063156]
  7. Stocchi F, De Pandis MF: Utility of tolcapone in fluctuating Parkinson's disease. Clin Interv Aging. 2006;1(4):317-25. [PubMed:18046910]
  8. 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:12538800]
  9. Tai CH, Wu RM: Catechol-O-methyltransferase and Parkinson's disease. Acta Med Okayama. 2002 Feb;56(1):1-6. [PubMed:11873938]
  10. Kaakkola S: Clinical pharmacology, therapeutic use and potential of COMT inhibitors in Parkinson's disease. Drugs. 2000 Jun;59(6):1233-50. [PubMed:10882160]
  11. Ruottinen HM, Rinne UK: COMT inhibition in the treatment of Parkinson's disease. J Neurol. 1998 Nov;245(11 Suppl 3):P25-34. [PubMed:9808337]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Drug created on June 13, 2005 07:24 / Updated on November 07, 2017 01:36