Ethotoin

Identification

Summary

Ethotoin is a hydantoin antiepileptic used to control tonic-clonic and complex partial seizures.

Brand Names
Peganone
Generic Name
Ethotoin
DrugBank Accession Number
DB00754
Background

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.

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 204.2252
Monoisotopic: 204.089877638
Chemical Formula
C11H12N2O2
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

Pharmacology

Indication

For the control of tonic-clonic (grand mal) and complex partial (psychomotor) seizures.

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Treatment ofGeneralised tonic-clonic seizure••••••••••••
Treatment ofPartial complex seizure••••••••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

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.

Mechanism of action

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 inhibits nerve impulses in the motor cortex by lowering sodium ion influx, limiting tetanic stimulation.

TargetActionsOrganism
ASodium channel protein type 5 subunit alpha
inhibitor
Humans
UNuclear receptor subfamily 1 group I member 2
activator
Humans
Absorption

Fairly rapidly absorbed, however, the extent of oral absorption is not known.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

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

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Route of elimination

Not Available

Half-life

3 to 9 hours

Clearance

Not Available

Adverse Effects
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Toxicity

Symptoms of overdose include drowsiness, loss of or impaired muscle coordination, nausea, visual disturbance, and, at very high doses, coma.

Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of CNS depression can be increased when Ethotoin is combined with 1,2-Benzodiazepine.
AcenocoumarolThe therapeutic efficacy of Acenocoumarol can be increased when used in combination with Ethotoin.
AcetazolamideThe risk or severity of CNS depression can be increased when Ethotoin is combined with Acetazolamide.
AcetophenazineThe risk or severity of CNS depression can be increased when Ethotoin is combined with Acetophenazine.
AgomelatineThe risk or severity of CNS depression can be increased when Ethotoin is combined with Agomelatine.
Food Interactions
  • Take after a meal. This may reduce gastrointestinal upset.

Products

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International/Other Brands
Accenon (Dainippon Sumitomo) / Pegoanone
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
PeganoneTablet250 mg/1OralRECORDATI RARE DISEASES, INC.1957-04-22Not applicableUS flag
PeganoneTablet250 mg/1OralLundbeck Inc.1957-04-222013-04-22US flag
PeganoneTablet250 mg/1OralRECORDATI RARE DISEASES, INC.1957-04-222018-08-31US flag

Categories

ATC Codes
N03AB01 — Ethotoin
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This 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.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azolidines
Sub Class
Imidazolidines
Direct Parent
Phenylhydantoins
Alternative Parents
Phenylimidazolidines / Alpha amino acids and derivatives / N-acyl ureas / Benzene and substituted derivatives / Dicarboximides / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
show 1 more
Substituents
5-phenylhydantoin / Alpha-amino acid or derivatives / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbonic acid derivative / Carbonyl group / Carboxylic acid derivative / Dicarboximide / Hydrocarbon derivative
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazolidine-2,4-dione (CHEBI:4888)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
46QG38NC4U
CAS number
86-35-1
InChI Key
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

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. [Article]
Human Metabolome Database
HMDB0014892
KEGG Drug
D00708
KEGG Compound
C07839
PubChem Compound
3292
PubChem Substance
46504521
ChemSpider
3176
BindingDB
50239975
RxNav
4136
ChEBI
4888
ChEMBL
CHEMBL1095
Therapeutic Targets Database
DAP000512
PharmGKB
PA164768735
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Ethotoin

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount

Pharmacoeconomics

Manufacturers
  • Lundbeck inc
Packagers
  • Abbott Laboratories Ltd.
  • Kaiser Foundation Hospital
  • Lundbeck Inc.
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.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)94 °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)11.18Chemaxon
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
Polarizability20.99 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleNoChemaxon
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)

Spectra

Mass Spec (NIST)
Download (8.5 KB)
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-053f-4900000000-890da1feecbdd89e1320
GC-MS Spectrum - EI-BGC-MSsplash10-0udi-6980000000-86b5edde33787fa5b3d5
GC-MS Spectrum - EI-BGC-MSsplash10-0zfr-4920000000-137fae4223f8b51dd5cd
GC-MS Spectrum - CI-BGC-MSsplash10-0a4i-1190000000-3ade8f65bbabe08f852a
GC-MS Spectrum - CI-BGC-MSsplash10-0udi-1190000000-56ad3615dcbc3fbecdbc
Mass Spectrum (Electron Ionization)MSsplash10-0udi-6920000000-01714c9dcd6c4cf02362
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSsplash10-0a4i-1900000000-f71513d432cabc6ae596
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-1900000000-f71513d432cabc6ae596
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-0090000000-2a390533fdeded788fe0
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0ul9-6960000000-b960d066cdf3d684bb2e
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a6u-7930000000-bde66dbfa629a95b7882
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0006-9200000000-9953ab20e67b9da7c850
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0kdl-9600000000-9599b14de8d47ea6243a
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0ukc-9800000000-82c39756af3c055baef7
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-152.8242228
predicted
DarkChem Lite v0.1.0
[M-H]-143.20692
predicted
DeepCCS 1.0 (2019)
[M+H]+153.7248228
predicted
DarkChem Lite v0.1.0
[M+H]+145.6025
predicted
DeepCCS 1.0 (2019)
[M+Na]+153.2868228
predicted
DarkChem Lite v0.1.0
[M+Na]+151.61118
predicted
DeepCCS 1.0 (2019)

Targets

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insights and accelerate drug research.
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Kind
Protein
Organism
Humans
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 pr...
Gene Name
SCN5A
Uniprot ID
Q14524
Uniprot Name
Sodium channel protein type 5 subunit alpha
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. [Article]
  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. [Article]
  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. [Article]
  4. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Activator
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
Gene Name
NR1I2
Uniprot ID
O75469
Uniprot Name
Nuclear receptor subfamily 1 group I member 2
Molecular Weight
49761.245 Da
References
  1. Kobayashi K, Yamagami S, Higuchi T, Hosokawa M, Chiba K: Key structural features of ligands for activation of human pregnane X receptor. Drug Metab Dispos. 2004 Apr;32(4):468-72. [Article]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
Serine-type endopeptidase inhibitor activity
Specific Function
Major thyroid hormone transport protein in serum.
Gene Name
SERPINA7
Uniprot ID
P05543
Uniprot Name
Thyroxine-binding globulin
Molecular Weight
46324.12 Da
References
  1. CYTOMEL (liothyronine) FDA label [File]

Drug created at June 13, 2005 13:24 / Updated at December 02, 2023 06:55