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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
(+-)-3-Ethyl-5-phenylhydantoin
1-Ethyl-2,5-dioxo-4-phenylimidazolidine
3-Ethyl-5-phenyl-2,4-imidazolidinedione
3-Ethyl-5-phenyl-imidazolidine-2,4-dione
3-Ethyl-5-phenylhydantoin
3-Ethyl-5-phenylimidazolidin-2,4-dione
Ethotoin
Ethotoïne
Ethotoinum
Etotoina
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Peganonetablet250 mg/1oralRECORDATI RARE DISEASES, INC.1957-04-22Not applicableUs
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AccenonDainippon Sumitomo
PegoanoneNot Available
Brand mixturesNot Available
SaltsNot Available
Categories
UNII46QG38NC4U
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as phenylhydantoins. These are heterocyclic aromatic compounds containing an imiazolidinedione moiety substituted by a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassAzolidines
Sub ClassImidazolidines
Direct ParentPhenylhydantoins
Alternative Parents
Substituents
  • 5-phenylhydantoin
  • Phenylimidazolidine
  • Ureide
  • Benzenoid
  • Monocyclic benzene moiety
  • Urea
  • Tertiary amine
  • Carboxamide group
  • Azacycle
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
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.
Related Articles
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
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9936
Caco-2 permeable+0.5629
P-glycoprotein substrateNon-substrate0.592
P-glycoprotein inhibitor INon-inhibitor0.8358
P-glycoprotein inhibitor IINon-inhibitor0.9401
Renal organic cation transporterNon-inhibitor0.8532
CYP450 2C9 substrateNon-substrate0.7507
CYP450 2D6 substrateNon-substrate0.9115
CYP450 3A4 substrateNon-substrate0.7383
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.914
CYP450 2D6 inhibitorNon-inhibitor0.9619
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8591
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8483
Ames testNon AMES toxic0.7056
CarcinogenicityNon-carcinogens0.8655
BiodegradationNot ready biodegradable0.8423
Rat acute toxicity2.1653 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.886
hERG inhibition (predictor II)Non-inhibitor0.8724
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Lundbeck inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral250 mg/1
Prices
Unit descriptionCostUnit
Peganone 250 mg tablet1.33USD tablet
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 Solubility2.38 mg/mLALOGPS
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 Area49.41 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity55.05 m3·mol-1ChemAxon
Polarizability20.68 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Download (8.5 KB)
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
MSMass Spectrum (Electron Ionization)splash10-0udi-6920000000-01714c9dcd6c4cf02362View in MoNA
References
Synthesis Reference

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

General References
  1. SCHWADE ED, RICHARDS RK, EVERETT GM: Peganone, a new antiepileptic drug. Dis Nerv Syst. 1956 May;17(5):155-8. [PubMed:13317788 ]
External Links
ATC CodesN03AB01
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcenocoumarolEthotoin may increase the anticoagulant activities of Acenocoumarol.
AzelastineEthotoin may increase the central nervous system depressant (CNS depressant) activities of Azelastine.
BaclofenThe risk or severity of adverse effects can be increased when Baclofen is combined with Ethotoin.
BrimonidineBrimonidine may increase the central nervous system depressant (CNS depressant) activities of Ethotoin.
BuprenorphineEthotoin may increase the central nervous system depressant (CNS depressant) activities of Buprenorphine.
DicoumarolEthotoin may increase the anticoagulant activities of Dicoumarol.
DoxylamineDoxylamine may increase the central nervous system depressant (CNS depressant) activities of Ethotoin.
DronabinolDronabinol may increase the central nervous system depressant (CNS depressant) activities of Ethotoin.
DroperidolDroperidol may increase the central nervous system depressant (CNS depressant) activities of Ethotoin.
EthanolEthotoin may increase the central nervous system depressant (CNS depressant) activities of Ethanol.
HydrocodoneEthotoin may increase the central nervous system depressant (CNS depressant) activities of Hydrocodone.
HydroxyzineHydroxyzine may increase the central nervous system depressant (CNS depressant) activities of Ethotoin.
LorazepamThe risk or severity of adverse effects can be increased when Lorazepam is combined with Ethotoin.
Magnesium SulfateMagnesium Sulfate may increase the central nervous system depressant (CNS depressant) activities of Ethotoin.
MefloquineThe therapeutic efficacy of Ethotoin can be decreased when used in combination with Mefloquine.
MethotrimeprazineEthotoin may increase the central nervous system depressant (CNS depressant) activities of Methotrimeprazine.
MetyrosineEthotoin may increase the sedative activities of Metyrosine.
MianserinThe therapeutic efficacy of Ethotoin can be decreased when used in combination with Mianserin.
MinocyclineMinocycline may increase the central nervous system depressant (CNS depressant) activities of Ethotoin.
MirtazapineEthotoin may increase the central nervous system depressant (CNS depressant) activities of Mirtazapine.
NabiloneNabilone may increase the central nervous system depressant (CNS depressant) activities of Ethotoin.
OrlistatThe serum concentration of Ethotoin can be decreased when it is combined with Orlistat.
OrphenadrineEthotoin may increase the central nervous system depressant (CNS depressant) activities of Orphenadrine.
ParaldehydeEthotoin may increase the central nervous system depressant (CNS depressant) activities of Paraldehyde.
ParoxetineThe risk or severity of adverse effects can be increased when Ethotoin is combined with Paroxetine.
PerampanelPerampanel may increase the central nervous system depressant (CNS depressant) activities of Ethotoin.
PramipexoleEthotoin may increase the sedative activities of Pramipexole.
RopiniroleEthotoin may increase the sedative activities of Ropinirole.
RotigotineEthotoin may increase the sedative activities of Rotigotine.
RufinamideThe risk or severity of adverse effects can be increased when Rufinamide is combined with Ethotoin.
Sodium oxybateSodium oxybate may increase the central nervous system depressant (CNS depressant) activities of Ethotoin.
SuvorexantEthotoin may increase the central nervous system depressant (CNS depressant) activities of Suvorexant.
TapentadolTapentadol may increase the central nervous system depressant (CNS depressant) activities of Ethotoin.
ThalidomideEthotoin may increase the central nervous system depressant (CNS depressant) activities of Thalidomide.
WarfarinEthotoin may increase the anticoagulant activities of Warfarin.
ZolpidemEthotoin may increase the central nervous system depressant (CNS depressant) activities of Zolpidem.
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
inhibitor
General Function:
Voltage-gated sodium channel activity involved in sa node cell action potential
Specific Function:
This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient. It is a tetrodotoxin-resistant Na(+) channel isoform. This channel is respon...
Gene Name:
SCN5A
Uniprot ID:
Q14524
Molecular Weight:
226937.475 Da
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:17139284 ]
  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:17016423 ]
  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:15066664 ]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:
CYP2C19
Uniprot ID:
P33261
Molecular Weight:
55930.545 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 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23