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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
(+-)-3-Ethyl-5-phenylhydantoinNot AvailableNot Available
1-Ethyl-2,5-dioxo-4-phenylimidazolidineNot AvailableNot Available
3-Ethyl-5-phenyl-2,4-imidazolidinedioneNot AvailableNot Available
3-Ethyl-5-phenyl-imidazolidine-2,4-dioneNot AvailableNot Available
3-Ethyl-5-phenylhydantoinNot AvailableNot Available
3-Ethyl-5-phenylimidazolidin-2,4-dioneNot AvailableNot Available
EthotoinGermanINN
EthotoïneFrenchINN
EthotoinumLatinINN
EtotoinaSpanishINN
SaltsNot Available
Brand names
NameCompany
AccenonDainippon Sumitomo
PeganoneLundbeck
PegoanoneNot Available
Brand mixturesNot Available
Categories
CAS number86-35-1
WeightAverage: 204.2252
Monoisotopic: 204.089877638
Chemical FormulaC11H12N2O2
InChI KeySZQIFWWUIBRPBZ-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
Not Available
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 Reference

Close, W.J.; U.S. Patent 2,793,157; May 21, 1957; assigned to Abbott Laboratories.

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

Targets

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

Enzymes

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

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Drug created on June 13, 2005 07:24 / Updated on April 22, 2014 10:40