DrugBank: Ethotoin (DB00754)

targets (1) enzymes (1)

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.

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Ethotoine [INN-French]
Ethotoinum [INN-Latin]
Etotoina [INN-Spanish]

Salts

Not Available

Brand names

Name	Company
Accenon
Peganone
Pegoanone

Brand mixtures

Not Available

Categories

Anticonvulsants

CAS number

86-35-1

Weight

Average: 204.2252
Monoisotopic: 204.089877638

Chemical Formula

C₁₁H₁₂N₂O₂

InChI Key

InChIKey=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)

Plain Text

IUPAC Name

3-ethyl-5-phenylimidazolidine-2,4-dione

SMILES

CCN1C(=O)NC(C1=O)C1=CC=CC=C1

Plain Text

Mass Spec

show (8.5 KB)

Taxonomy

Kingdom

Organic

Classes

Phenethylamines

Substructures

Imidazolidinediones
Amino Ketones
Benzene and Derivatives
Ureas and Derivatives
Imidazolidines
Phenethylamines
Heterocyclic compounds
Aromatic compounds
Carboxamides and Derivatives
Carboxylic Acids and Derivatives

Pharmacology

Indication

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

Pharmacodynamics

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.

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

Pharmacoeconomics

Manufacturers

Lundbeck inc

Packagers

Abbott Laboratories Ltd.
Kaiser Foundation Hospital
Lundbeck Inc.

Dosage forms

Form	Route	Strength
Tablet	Oral

Prices

Unit description	Cost	Unit
Peganone 250 mg tablet	1.33 USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

solid

Experimental Properties

Property	Value	Source
melting point	94 °C	PhysProp
water solubility	5280 mg/L	Not Available
logP	1.05	SANGSTER (1994)

Predicted Properties

Property	Value	Source
water solubility	2.38e+00 g/l	ALOGPS
logP	1.11	ALOGPS
logP	1.07	ChemAxon
logS	-1.9	ALOGPS
pKa (strongest acidic)	11.29	ChemAxon
pKa (strongest basic)	-8.4	ChemAxon
physiological charge	0	ChemAxon
hydrogen acceptor count	2	ChemAxon
hydrogen donor count	1	ChemAxon
polar surface area	49.41	ChemAxon
rotatable bond count	2	ChemAxon
refractivity	55.05	ChemAxon
polarizability	20.68	ChemAxon

References

Synthesis Reference

Not Available

General Reference

SCHWADE ED, RICHARDS RK, EVERETT GM: Peganone, a new antiepileptic drug. Dis Nerv Syst. 1956 May;17(5):155-8. Pubmed

External Links

Resource	Link
KEGG Drug	D00708
KEGG Compound	C07839
PubChem Compound	3292
PubChem Substance	46504521
ChemSpider	3176
ChEBI	4888
ChEMBL	4888
Therapeutic Targets Database	DAP000512
PharmGKB	PA164768735
RxList	http://www.rxlist.com/cgi/generic3/peganone.htm
Drugs.com	http://www.drugs.com/cdi/ethotoin.html
PDRhealth	http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/peg1665.shtml
Wikipedia	http://en.wikipedia.org/wiki/Ethotoin

ATC Codes

N03AB01

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

Not Available

Interactions

Drug Interactions

Drug	Interaction
Alprazolam	Ethotoin may increase the metabolism of alprazolam via CYP3A4.
Aminophylline	Decreased effect of both products
Amiodarone	Increases the effect of hydantoin
Aprepitant	The CYP3A4 inducer, ethotoin, may decrease the effect of aprepitant.
Betamethasone	The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, betamethasone.
Capecitabine	Capecitabine increases the effect of hydantoin
Chloramphenicol	Increases phenytoin, modifies chloramphenicol
Chlordiazepoxide	Ethotoin may increase the metabolism of chlordiazepoxide via CYP3A4.
Chlorpheniramine	The antihistamine increases the effect of hydantoin
Cimetidine	Increases the effect of hydantoin
Ciprofloxacin	Decreases the hydantoin effect
Clomifene	The enzyme inducer, ethotoin, decreases the effect of the hormone agent, clomifene.
Clorazepate	Ethotoin may increase the metabolism of clorazepate via CYP3A4.
Clozapine	Hydantoin decreases the effect of clozapine
Conjugated Estrogens	The enzyme inducer, ethotoin, decreases the effect of the hormone agent, conjugated estrogens.
Cyclosporine	The hydantoin decreases the effect of cyclosporine
Dexamethasone	The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, dexamethasone.
Diazepam	Ethotoin may increase the metabolism of diazepam via CYP3A4.
Diethylstilbestrol	The enzyme inducer, ethotoin, decreases the effect of the hormone agent, diethylstilbestrol.
Disopyramide	The hydantoin decreases the effect of disopyramide
Disulfiram	Increases the effect of phenytoin
Doxycycline	The anticonvulsant, ethotoin, decreases the effect of doxycycline.
Estradiol	The enzyme inducer, ethotoin, decreases the effect of the hormone agent, estradiol.
Ethinyl Estradiol	This product may cause a slight decrease of contraceptive effect
Felbamate	Increased phenytoin levels and decreased felbamate levels
Felodipine	The hydantoin decreases the effect of felodipine
Fluconazole	Increases the effect of hydantoin
Fludrocortisone	The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, fludrocortisone.
Fluorouracil	Fluorouracil increases the effect of hydantoin
Fluoxetine	Fluoxetine increases the effect of phenytoin
Flurazepam	Ethotoin may increase the metabolism of flurazepam via CYP3A4.
Fluvoxamine	Increases the effect of hydantoin
Folic Acid	Folic acid decreases the levels of hydantoin
Furosemide	The hydantoin decreases the effect of furosemide
Gabapentin	Increases the effect of hydantoin
Gefitinib	The CYP3A4 inducer, ethotoin, may decrease the serum concentration and therapeutic effects of gefitinib.
Hydrocortisone	The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, hydrocortisone.
Imatinib	The hydantoin decreases the levels of imatinib
Isoniazid	Isoniazid increases the effect of phenytoin in 20% of patients
Itraconazole	Phenytoin decreases the effect of itraconazole
Lamotrigine	Phenytoin may reduce levels of lamotrigine
Levonorgestrel	Phenytoin decreases the contraceptive effect
Mebendazole	The hydantoin decreases the efficiency of mebendazole
Medroxyprogesterone	The enzyme inducer, ethotoin, decreases the effect of the hormone agent, medroxyprogesterone.
Megestrol	The enzyme inducer, ethotoin, decreases the effect of the hormone agent, megestrol.
Methadone	The hydantoin decreases the effect of methadone
Methotrexate	The antineoplasic agent decreases the effect of hydantoin
Methoxsalen	The hydantoin decreases the effect of psoralene
Mexiletine	The hydantoin decreases the effect of mexiletine
Midazolam	Ethotoin may increase the metabolism of midazolam via CYP3A4.
Mirtazapine	The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
Norethindrone	This product may cause a slight decrease of contraceptive effect
Omeprazole	Omeprazole increases the effect of hydantoin
Oxcarbazepine	Oxcarbazepine increases the effect of hydantoin
Oxtriphylline	Decreased effect of both products
Oxyphenbutazone	The NSAID, oxyphenbutazone, may increase the hydantoin effect of ethotoin.
Phenylbutazone	The NSAID, phenylbutazone, may increase the hydantoin effect of ethotoin.
Prednisolone	The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, prednisolone.
Prednisone	The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, prednisone.
Quetiapine	Phenytoin decreases the effect of quetiapine
Rifampin	Rifampin decreases the effect of the hydantoin
Theophylline	Decreased effect of both products
Ticlopidine	Ticlopidine increases the effect of hydantoin
Triamcinolone	The enzyme inducer, ethotoin, may decrease the effect of the corticosteroid, triamcinolone.
Triazolam	Ethotoin may increase the metabolism of triazolam via CYP3A4.
Triprolidine	The CNS depressants, Triprolidine and Ethotoin, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.

Food Interactions

Not Available

Targets
1. Sodium channel protein type 5 subunit alpha Pharmacological action: yes Actions: inhibitor 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 responsible for the initial upstroke of the action potential in the electrocardiogram Organism class: human UniProt ID: Q14524 Gene: SCN5A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed 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 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 Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

Targets

1. Sodium channel protein type 5 subunit alpha

Pharmacological action: yes
Actions: inhibitor

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 responsible for the initial upstroke of the action potential in the electrocardiogram

Organism class: human
UniProt ID: Q14524 Link_out

Gene: SCN5A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
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
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
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 Actions: inhibitor 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 UniProt ID: P33261 Gene: CYP2C19 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: 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

Enzymes

1. Cytochrome P450 2C19

Actions: inhibitor

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

UniProt ID: P33261 Link_out

Gene: CYP2C19 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

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 February 08, 2013 16:19