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Identification
NameEthotoin
Accession NumberDB00754  (APRD00962)
Typesmall molecule
Groupsapproved
Description

Ethotoin is a hydantoin derivative and anticonvulsant. Ethotoin exerts an antiepileptic effect without causing general central nervous system depression. The mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges. Ethotoin is no longer commonly used.

Structure
Thumb
Synonyms
SynonymLanguageCode
EthotoinGermanINN
EthotoïneFrenchINN
EthotoinumLatinINN
EtotoinaSpanishINN
SaltsNot Available
Brand names
NameCompany
AccenonDainippon Sumitomo
PeganoneOvation Pharmaceuticals
PegoanoneNot Available
Brand mixturesNot Available
Categories
CAS number86-35-1
WeightAverage: 204.2252
Monoisotopic: 204.089877638
Chemical FormulaC11H12N2O2
InChI KeyInChIKey=SZQIFWWUIBRPBZ-UHFFFAOYSA-N
InChI
InChI=1S/C11H12N2O2/c1-2-13-10(14)9(12-11(13)15)8-6-4-3-5-7-8/h3-7,9H,2H2,1H3,(H,12,15)
IUPAC Name
3-ethyl-5-phenylimidazolidine-2,4-dione
SMILES
CCN1C(=O)NC(C1=O)C1=CC=CC=C1
Mass Specshow(8.5 KB)
Taxonomy
KingdomOrganic Compounds
SuperclassHeterocyclic Compounds
ClassAzolidines
SubclassImidazolidines
Direct parentPhenylhydantoins
Alternative parentsPhenylimidazolidines; Ureides; N-substituted Carboxylic Acid Imides; Benzene and Substituted Derivatives; Tertiary Carboxylic Acid Amides; Tertiary Amines; Carboxylic Acids; Polyamines
Substituentsphenylimidazolidine; ureide; carboxylic acid imide, n-substituted; benzene; tertiary carboxylic acid amide; carboxamide group; tertiary amine; carboxylic acid derivative; carboxylic acid; polyamine; organonitrogen compound; amine
Classification descriptionThis compound belongs to the phenylhydantoins. These are heterocyclic aromatic compounds containing an imiazolidinedione moiety substituted by a phenyl group.
Pharmacology
IndicationFor the control of tonic-clonic (grand mal) and complex partial (psychomotor) seizures.
PharmacodynamicsEthotoin is a hydantoin derivative and anticonvulsant. Ethotoin exerts an antiepileptic effect without causing general central nervous system depression. The mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges.
Mechanism of actionThe mechanism of action is probably very similar to that of phenytoin. The latter drug appears to stabilize rather than to raise the normal seizure threshold, and to prevent the spread of seizure activity rather than to abolish the primary focus of seizure discharges. Ethotoin inhibits nerve impulses in the motor cortex by lowering sodium ion influx, limiting tetanic stimulation.
AbsorptionFairly rapidly absorbed, however, the extent of oral absorption is not known.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic. The drug exhibits saturable metabolism with respect to the formation of N-deethyl and p-hydroxyl-ethotoin, the major metabolites.

SubstrateEnzymesProduct
Ethotoin
    p-Hydroxyl-ethotoinDetails
    Route of eliminationNot Available
    Half life3 to 9 hours
    ClearanceNot Available
    ToxicitySymptoms of overdose include drowsiness, loss of or impaired muscle coordination, nausea, visual disturbance, and, at very high doses, coma.
    Affected organisms
    • Humans and other mammals
    PathwaysNot Available
    SNP Mediated EffectsNot Available
    SNP Mediated Adverse Drug ReactionsNot Available
    ADMET
    Predicted ADMET features
    Property Value Probability
    Human Intestinal Absorption + 1.0
    Blood Brain Barrier + 0.9936
    Caco-2 permeable + 0.5629
    P-glycoprotein substrate Non-substrate 0.592
    P-glycoprotein inhibitor I Non-inhibitor 0.8358
    P-glycoprotein inhibitor II Non-inhibitor 0.9401
    Renal organic cation transporter Non-inhibitor 0.8532
    CYP450 2C9 substrate Non-substrate 0.7507
    CYP450 2D6 substrate Non-substrate 0.9115
    CYP450 3A4 substrate Non-substrate 0.7383
    CYP450 1A2 substrate Non-inhibitor 0.9045
    CYP450 2C9 substrate Non-inhibitor 0.914
    CYP450 2D6 substrate Non-inhibitor 0.9619
    CYP450 2C19 substrate Non-inhibitor 0.9025
    CYP450 3A4 substrate Non-inhibitor 0.8591
    CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8483
    Ames test Non AMES toxic 0.7056
    Carcinogenicity Non-carcinogens 0.8655
    Biodegradation Not ready biodegradable 0.8423
    Rat acute toxicity 2.1653 LD50, mol/kg Not applicable
    hERG inhibition (predictor I) Weak inhibitor 0.886
    hERG inhibition (predictor II) Non-inhibitor 0.8724
    Pharmacoeconomics
    Manufacturers
    • Lundbeck inc
    Packagers
    Dosage forms
    FormRouteStrength
    TabletOral
    Prices
    Unit descriptionCostUnit
    Peganone 250 mg tablet1.33USDtablet
    DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
    PatentsNot Available
    Properties
    Statesolid
    Experimental Properties
    PropertyValueSource
    melting point94 °CPhysProp
    water solubility5280 mg/LNot Available
    logP1.05SANGSTER (1994)
    Predicted Properties
    PropertyValueSource
    water solubility2.38e+00 g/lALOGPS
    logP1.11ALOGPS
    logP1.07ChemAxon
    logS-1.9ALOGPS
    pKa (strongest acidic)11.29ChemAxon
    pKa (strongest basic)-8.4ChemAxon
    physiological charge0ChemAxon
    hydrogen acceptor count2ChemAxon
    hydrogen donor count1ChemAxon
    polar surface area49.41ChemAxon
    rotatable bond count2ChemAxon
    refractivity55.05ChemAxon
    polarizability20.68ChemAxon
    number of rings2ChemAxon
    bioavailability1ChemAxon
    rule of fiveYesChemAxon
    Ghose filterYesChemAxon
    Veber's ruleNoChemAxon
    MDDR-like ruleNoChemAxon
    Spectra
    SpectraNot Available
    References
    Synthesis ReferenceNot Available
    General Reference
    1. SCHWADE ED, RICHARDS RK, EVERETT GM: Peganone, a new antiepileptic drug. Dis Nerv Syst. 1956 May;17(5):155-8. Pubmed
    External Links
    ResourceLink
    KEGG DrugD00708
    KEGG CompoundC07839
    PubChem Compound3292
    PubChem Substance46504521
    ChemSpider3176
    ChEBI4888
    ChEMBLCHEMBL1095
    Therapeutic Targets DatabaseDAP000512
    PharmGKBPA164768735
    RxListhttp://www.rxlist.com/cgi/generic3/peganone.htm
    Drugs.comhttp://www.drugs.com/cdi/ethotoin.html
    PDRhealthhttp://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/peg1665.shtml
    WikipediaEthotoin
    ATC CodesN03AB01
    AHFS CodesNot Available
    PDB EntriesNot Available
    FDA labelNot Available
    MSDSNot Available
    Interactions
    Drug Interactions
    Drug
    AlprazolamEthotoin may increase the metabolism of alprazolam via CYP3A4.
    AminophyllineDecreased effect of both products
    AmiodaroneIncreases the effect of hydantoin
    AprepitantThe CYP3A4 inducer, ethotoin, may decrease the effect of aprepitant.
    BetamethasoneThe enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, betamethasone.
    CapecitabineCapecitabine increases the effect of hydantoin
    ChloramphenicolIncreases phenytoin, modifies chloramphenicol
    ChlordiazepoxideEthotoin may increase the metabolism of chlordiazepoxide via CYP3A4.
    ChlorphenamineThe antihistamine increases the effect of hydantoin
    CimetidineIncreases the effect of hydantoin
    CiprofloxacinDecreases the hydantoin effect
    ClomifeneThe enzyme inducer, ethotoin, decreases the effect of the hormone agent, clomifene.
    ClorazepateEthotoin may increase the metabolism of clorazepate via CYP3A4.
    ClozapineHydantoin decreases the effect of clozapine
    Conjugated EstrogensThe enzyme inducer, ethotoin, decreases the effect of the hormone agent, conjugated estrogens.
    CyclosporineThe hydantoin decreases the effect of cyclosporine
    DexamethasoneThe enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, dexamethasone.
    DiazepamEthotoin may increase the metabolism of diazepam via CYP3A4.
    DiethylstilbestrolThe enzyme inducer, ethotoin, decreases the effect of the hormone agent, diethylstilbestrol.
    DisopyramideThe hydantoin decreases the effect of disopyramide
    DisulfiramIncreases the effect of phenytoin
    DoxycyclineThe anticonvulsant, ethotoin, decreases the effect of doxycycline.
    EstradiolThe enzyme inducer, ethotoin, decreases the effect of the hormone agent, estradiol.
    Ethinyl EstradiolThis product may cause a slight decrease of contraceptive effect
    FelbamateIncreased phenytoin levels and decreased felbamate levels
    FelodipineThe hydantoin decreases the effect of felodipine
    FluconazoleIncreases the effect of hydantoin
    FludrocortisoneThe enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, fludrocortisone.
    FluorouracilFluorouracil increases the effect of hydantoin
    FluoxetineFluoxetine increases the effect of phenytoin
    FlurazepamEthotoin may increase the metabolism of flurazepam via CYP3A4.
    FluvoxamineIncreases the effect of hydantoin
    Folic AcidFolic acid decreases the levels of hydantoin
    FurosemideThe hydantoin decreases the effect of furosemide
    GabapentinIncreases the effect of hydantoin
    GefitinibThe CYP3A4 inducer, ethotoin, may decrease the serum concentration and therapeutic effects of gefitinib.
    HydrocortisoneThe enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, hydrocortisone.
    ImatinibThe hydantoin decreases the levels of imatinib
    IsoniazidIsoniazid increases the effect of phenytoin in 20% of patients
    ItraconazolePhenytoin decreases the effect of itraconazole
    LamotriginePhenytoin may reduce levels of lamotrigine
    LevonorgestrelPhenytoin decreases the contraceptive effect
    MebendazoleThe hydantoin decreases the efficiency of mebendazole
    Medroxyprogesterone AcetateThe enzyme inducer, ethotoin, decreases the effect of the hormone agent, medroxyprogesterone.
    Megestrol acetateThe enzyme inducer, ethotoin, decreases the effect of the hormone agent, megestrol.
    MethadoneThe hydantoin decreases the effect of methadone
    MethotrexateThe antineoplasic agent decreases the effect of hydantoin
    MethoxsalenThe hydantoin decreases the effect of psoralene
    MexiletineThe hydantoin decreases the effect of mexiletine
    MidazolamEthotoin may increase the metabolism of midazolam via CYP3A4.
    MirtazapineThe hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
    NorethindroneThis product may cause a slight decrease of contraceptive effect
    OmeprazoleOmeprazole increases the effect of hydantoin
    OxcarbazepineOxcarbazepine increases the effect of hydantoin
    OxtriphyllineDecreased effect of both products
    OxyphenbutazoneThe NSAID, oxyphenbutazone, may increase the hydantoin effect of ethotoin.
    PhenylbutazoneThe NSAID, phenylbutazone, may increase the hydantoin effect of ethotoin.
    PrednisoloneThe enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, prednisolone.
    PrednisoneThe enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, prednisone.
    QuetiapinePhenytoin decreases the effect of quetiapine
    RifampicinRifampin decreases the effect of the hydantoin
    TheophyllineDecreased effect of both products
    TiclopidineTiclopidine increases the effect of hydantoin
    TriamcinoloneThe enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, triamcinolone.
    TriazolamEthotoin may increase the metabolism of triazolam via CYP3A4.
    TriprolidineThe CNS depressants, Triprolidine and Ethotoin, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
    Food InteractionsNot Available

    1. Sodium channel protein type 5 subunit alpha

    Kind: protein

    Organism: Human

    Pharmacological action: yes

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Sodium channel protein type 5 subunit alpha Q14524 Details

    References:

    1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
    2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
    3. Lenkowski PW, Ko SH, Anderson JD, Brown ML, Patel MK: Block of human NaV1.5 sodium channels by novel alpha-hydroxyphenylamide analogues of phenytoin. Eur J Pharm Sci. 2004 Apr;21(5):635-44. Pubmed
    4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

    1. Cytochrome P450 2C19

    Kind: protein

    Organism: Human

    Pharmacological action: unknown

    Actions: inhibitor

    Components

    Name UniProt ID Details
    Cytochrome P450 2C19 P33261 Details

    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. Epub 2009 Nov 24. Pubmed

    Comments
    Drug created on June 13, 2005 07:24 / Updated on January 03, 2014 16:36