Identification

Name
Ethotoin
Accession Number
DB00754  (APRD00962)
Type
Small Molecule
Groups
Approved
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
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
PeganoneTablet250 mg/1OralLundbeck Inc.1957-04-222013-04-22Us
PeganoneTablet250 mg/1OralRecordati Rare Diseases Inc1957-04-222018-08-31Us
PeganoneTablet250 mg/1OralRecordati Rare Diseases Inc1957-04-22Not applicableUs
International/Other Brands
Accenon (Dainippon Sumitomo) / Pegoanone
Categories
UNII
46QG38NC4U
CAS number
86-35-1
Weight
Average: 204.2252
Monoisotopic: 204.089877638
Chemical Formula
C11H12N2O2
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

Pharmacology

Indication

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

Associated Conditions
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
Human
UNuclear receptor subfamily 1 group I member 2
activator
Human
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.

Route of elimination
Not Available
Half life

3 to 9 hours

Clearance
Not Available
Toxicity

Symptoms 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
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe therapeutic efficacy of (R)-warfarin can be increased when used in combination with Ethotoin.
(S)-WarfarinThe therapeutic efficacy of (S)-Warfarin can be increased when used in combination with Ethotoin.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Ethotoin is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3-isobutyl-1-methyl-7H-xanthineEthotoin may increase the excretion rate of 3-isobutyl-1-methyl-7H-xanthine which could result in a lower serum level and potentially a reduction in efficacy.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Ethotoin is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be increased when combined with Ethotoin.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Ethotoin is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe therapeutic efficacy of 4-hydroxycoumarin can be increased when used in combination with Ethotoin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Ethotoin is combined with 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of 5-androstenedione can be increased when combined with Ethotoin.
Food Interactions
Not Available

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
Human Metabolome Database
HMDB0014892
KEGG Drug
D00708
KEGG Compound
C07839
PubChem Compound
3292
PubChem Substance
46504521
ChemSpider
3176
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
ATC Codes
N03AB01 — Ethotoin

Clinical Trials

Clinical Trials
Not Available

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)11.29ChemAxon
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 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-MSNot Available
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
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0a4i-1900000000-f71513d432cabc6ae596

Taxonomy

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 / Phenylimidazolidine / Alpha-amino acid or derivatives / N-acyl urea / Ureide / Monocyclic benzene moiety / Benzenoid / Dicarboximide / Urea / Carbonic acid derivative
show 11 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
imidazolidine-2,4-dione (CHEBI:4888)

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 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. [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]
Kind
Protein
Organism
Human
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. [PubMed:15039302]

Drug created on June 13, 2005 07:24 / Updated on December 16, 2018 06:42