Search References Drug Actions/Targets About Access data Feedback
Sign In
mitontu@gmail.com
2021 MitoTox | (CC BY-NC 4.0)
Drug

D0121 | Tolcapone

Molecular Formula C14H11NO5
Molecular Weight 273.24
Structure
State solid
Clearance * 7 L/h
Volume of distribution * 9 L
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.
Protein binding > 99.9% (to serum albumin)
Half life 2-3.5 hours
Absorption Rapidly absorbed (absolute bioavailability is about 65%)
Description methyl-transferase inhibitors; inhibits the enzyme catechol-O-methyl transferase (COMT); uncoupler; contain the nitrophenol protonophore

N

N04BX01 Tolcapone


[N04BX] Other dopaminergic agents


[N04B] DOPAMINERGIC AGENTS


[N04] ANTI-PARKINSON DRUGS


[N] Nervous system

Toxicity Dose Time Species Model Method Action Positive criterion Reference
UNCOUPLING increase 35
ELECTROPHORETIC UNCOUPLING 278
ASSOCIATE WITH UNCOUPLING rat liver mitochondria RST assay( Respiratory Screening Technology)-measurement of oxygen consumption in isolated mitochondria using a phosphorescent oxygen-sensitive probe A65N-1 affect 204
MEMBRANE POTENTIAL 3.9 µM 30 mins mouse liver mitochondria Rh123 fluorescence (excitation 485 nm, emission 535 nm) are recorded using a fluorescence multi-well plate reader (mCICCP (20 µM) treatments was considered as the 100% baseline for ΔΨm loss) decrease EC20 36
RESPIRATION ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. Negative EC20 36
RESPIRATION ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. Negative EC20 36
OXYGEN CONSUMPTION RATE (OCR) 3.7 μM 2 minutes human HepG2 Measurement of OCR increase EC50 7
ECAR 3.7 μM 2 minutes human HepG2 Measurement of ECAR increase EC50 7
SWELLING > 400 µM 30 mins mouse liver mitochondria swelling assay: Absorbance at 545 nm using a fluorescence multi-well plate reader (CaCl2 (50 µM) was considered as the 100% baseline for the swelling ) increase EC20 36

Target Dose Time Species Model Method Action Positive criterion Reference
NADH:ubiquinone reductase ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Rotenone (2µM) was used as 100% baseline for complex I inhibition. Negative EC20 36
Succinate dehydrogenase ND 60 mins mouse liver mitochondria Oxygen consumption was monitored with 50nM MitoXpress ( an oxygen-sensitive phosphorescent dye) using a spectrofluorimeter (Tecan Infinite 200; λExcitation 380nm; λEmission 650nm). Oligomycin A (1µM) was used as 100% baseline for complex II inhibition. Negative EC20 36
Cytochrome c > 400 µM 30 mins mouse liver mitochondria Cytochrome c release was evaluated using ELISA kit ( 20 µg/ml Alamethicin was used as 100% baseline) release EC20 36

Pictogram Signal Statements Precautionary Statement Codes
Warning

Aggregated GHS information provided by 39 companies from 1 notifications to the ECHA C&L Inventory.


H400 (100%): Very toxic to aquatic life [Warning Hazardous to the aquatic environment, acute hazard]


Information may vary between notifications depending on impurities, additives, and other factors. The percentage value in parenthesis indicates the notified classification ratio from companies that provide hazard codes. Only hazard codes with percentage values above 10% are shown.


 P273, P391, and P501; (The corresponding statement to each P-code can be found at the GHS Classification page.)

  • Parkinson's disease

  • Parkinsonism

  • Abdominal pain

  • Abnormal dreams

  • Agitation

  • Alopecia

  • Arthritis

  • Asthenia

  • Body temperature increased

  • Cataract

  • Chest discomfort

  • Chest pain

  • Chromaturia

  • Confusional state

  • Constipation

  • Decreased appetite

  • Diarrhoea

  • Discomfort

  • Dizziness

  • Dry mouth

  • Dyskinesia

  • Dyspepsia

  • Dyspnoea

  • Endophthalmitis

  • Euphoric mood

  • Fall

  • Fatigue

  • Feeling abnormal

  • Flatulence

  • Gastrointestinal pain

  • Haemoglobin

  • Haemorrhage

  • Hallucination

  • Headache

  • Hyperhidrosis

  • Hyperkinesia

  • Hypertonia

  • Hypokinesia

  • Hypotension

  • Ill-defined disorder

  • Influenza

  • Irritability

  • Loss of consciousness

  • Malaise

  • Mental retardation

  • Micturition disorder

  • Muscle spasms

  • Musculoskeletal stiffness

  • Nausea

  • Neck pain

  • Neoplasm skin

  • Ocular hyperaemia

  • Panic reaction

  • Paraesthesia

  • Shock

  • Sinus congestion

  • Sleep disorder

  • Somnolence

  • Syncope

  • Upper respiratory tract infection

  • Urinary tract infection

  • Uterine neoplasm

  • Vomiting

    • (3,4-Dihydroxy-5-nitro-phenyl)-p-tolyl-methanone (3,4-Dihydroxy-5-nitrophenyl)(4-methylphenyl)methanone (3,4-dihydroxy-5-nitrophenyl)(p-tolyl)methanone
    (3,4-dihydroxy-5-nitrophenyl)-(4-methylphenyl)methanone 134308-13-7 3,4-Dihydroxy-4'-methyl-5-nitrobenzophenone
    3,4-dihydroxy-5'-methyl-5-nitrobenzophenone 3,4-dihydroxy-5-nitro-4'-methylbenzophenone 308T137
    3s68 4'-methyl-3,4-dihydroxy-5-nitrobenzophenone 5-[(4-METHYLPHENYL)CARBONYL]-3-NITROBENZENE-1,2-DIOL
    AB0012754 AB01275441-01 AB01275441_02
    AC-791 AK671145 AKOS015902328
    API0004441 AS-7085 AX8154334
    BCP09156 BDBM50108877 BG0651
    BIDD:GT0032 BRD-K10852020-001-01-1 C-17206
    C07949 C14H11NO5 CAS-134308-13-7
    CC-35089 CCG-221217 CCRIS 7904
    CHEBI:63630 CHEMBL1324 CIF6334OLY
    CS-1173 CTK8E7392 D00786
    DB-013561 DB00323 DSSTox_CID_3685
    DSSTox_GSID_23685 DSSTox_RID_77146 DTXSID3023685
    EBD47899 FT-0082597 FT-0631149
    GTPL6646 HMS2089K14 HMS3652M17
    HMS3715D16 HY-17406 InChI=1/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,1H
    KS-00000XJL KS-1314 LS-91226
    MFCD00866569 MIQPIUSUKVNLNT-UHFFFAOYSA-N MLS006012044
    Methanone, (3,4-dihydroxy-5-nitrophenyl)(4-methylphenyl)- Methanone,(3,4-dihydroxy-5-nitrophenyl)(4-methylphenyl) NCGC00181767-01
    NCGC00181767-02 NCGC00181767-03 NCGC00255188-01
    Q-201840 Q413840 RT-016044
    Ro 40-7592 Ro-40-7592 Ro-407592
    SCHEMBL33869 SMR001614567 SR-05000001444
    SR-05000001444-1 SW219511-1 TCW
    Talcapone Tasmar Tasmar (TN)
    Tolcapon Tolcapona Tolcapone
    Tolcapone (JAN/USAN/INN) Tolcapone [USAN:INN] Tolcapone [USAN:USP:INN:BAN]
    Tolcapone, >=98% (HPLC) Tolcapone, United States Pharmacopeia (USP) Reference Standard Tolcaponum
    Tox21_112963 Tox21_112963_1 Tox21_302414
    UNII-CIF6334OLY W-5146 ZINC35342789
    s4021

    DrugBank Name Tolcapone
    DrugBank DB00323
    CAS Number 1246816-93-2, 134308-13-7
    PubChem Compound 4659569
    KEGG Compound ID C07949
    KEGG Drug D00786
    PubChem.Substance 46504932
    ChEBI 63630
    PharmGKB PA451720
    ChemSpider 3848682
    BindingDB 50108877.0
    TTD DAP000607
    Wikipedia Tolcapone
    HET TCW
    DPD 11615

    1. Chan et al. (2005)
    2. Cohen, 2010