ETHOTOIN

US Previously Marketed

Details

Stereochemistry	RACEMIC
Molecular Formula	C11H12N2O2
Molecular Weight	204.2252
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN1C(=O)NC(C1=O)C2=CC=CC=C2

InChI

InChIKey=SZQIFWWUIBRPBZ-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: http://www.drugbank.ca/drugs/DB00754
Curator's Comment: Description was created based on several sources, including https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/010841s022lbl.pdf

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 inhibits nerve impulses in the motor cortex by lowering sodium ion influx, limiting tetanic stimulation. Ethotoin is used for the control of tonic-clonic (grand mal) and complex partial (psychomotor) seizures. Ethotoin is marketed as Peganone by Ovation.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Sodium channel protein type V alpha subunit 49 Target ID: CHEMBL1980 Sources: http://www.drugbank.ca/drugs/DB00754	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Epilepsy 121 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/010841s022lbl.pdf	Primary		Approved 8429	PEGANONE Approved Use PEGANONE (ethotoin tablets, USP) is indicated for the control of tonic-clonic (grand mal) and complex partial (psychomotor) seizures. Launch Date 1957

C_max

Value	Dose	Co-administered	Analyte	Population
26.6 μg/mL EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1002/chir.530040303	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		ETHOTOIN, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
30.4 μg/mL EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1002/chir.530040303	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		ETHOTOIN, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

AUC

Value	Dose	Co-administered	Analyte	Population
510 μg × h/mL EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1002/chir.530040303	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		ETHOTOIN, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
580 pg × h/mL EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1002/chir.530040303	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:		ETHOTOIN, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

T_1/2

Value	Dose	Analyte	Population
12.35 h EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1002/chir.530040303	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	ETHOTOIN, (R)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED
5.11 h EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.410060506	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered:	ETHOTOIN serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN
12.28 h EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1002/chir.530040303	1000 mg single, oral dose: 1000 mg route of administration: Oral experiment type: SINGLE co-administered:	ETHOTOIN, (S)- plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE / MALE food status: FASTED

F_unbound

Value	Dose	Co-administered	Analyte	Population
58.8% EXPERIMENT https://onlinelibrary.wiley.com/doi/abs/10.1002/ana.410060506	25 mg/kg single, oral dose: 25 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		ETHOTOIN serum	Homo sapiens population: UNHEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737 inducer 781			inhibitor 1612

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1925	inducer 1573 Sources: https://www.wellrx.com/peganone/monographs/	strong

Drug as victim

Target	Modality	Activity	Metabolite	Clinical evidence
CYP3A4 1737	substrate 3367 Sources: https://www.pdr.net/drug-summary/Peganone-ethotoin-1253#:~:text=Additionally%2C%20ethotoin%20is%20a%20CYP3A4,increase%20plasma%20concentrations%20of%20ethotoin.	yes

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 1647	inhibitor 1626 Sources: https://bpspubs.onlinelibrary.wiley.com/doi/pdfdirect/10.1111/j.1476-5381.2011.01415.x#page=3

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4888	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4888
MolPort	MolPort-003-666-682	https://www.molport.com/shop/molecule-link/MolPort-003-666-682
eMolecules	33507655	https://www.emolecules.com/cgi-bin/more?vid=33507655

PubMed

Title	Date	PubMed
Peganone, a new antiepileptic drug.	1956 May	13317788
Key structural features of ligands for activation of human pregnane X receptor.	2004 Apr	15039302
Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis.	2015 May 18	25811541

Patents

Sample Use Guides

In Vivo Use Guide

PEGANONE (ethotoin tablets, USP) is administered orally in 4 to 6 divided doses daily. The drug should be taken after food, and doses should be spaced as evenly as practicable. Initial dosage should be conservative. For adults, the initial daily dose should be 1 g or less, with subsequent gradual dosage increases over a period of several days. The optimum dosage must be determined on the basis of individual response. The usual adult maintenance dose is 2 to 3 g daily. Less than 2 g daily has been found ineffective in most adults.

Route of Administration: Oral

In Vitro Use Guide

Ethotoin was not teratogenic at concentrations up to 2.93 mM in the sea urchin embryo

Name

Type

Language

ETHOTOIN

Official Name

English

ETHOTOIN [MART.]

Common Name

English

ethotoin [INN]

Common Name

English

ETHOTOIN [JAN]

Common Name

English

NSC-760074

Code

English

ETHOTOIN [MI]

Common Name

English

PEGANONE

Brand Name

English

ETHOTOIN [HSDB]

Common Name

English

(±)-3-ETHYL-5-PHENYLHYDANTOIN

Systematic Name

English

ETHOTOIN [USP MONOGRAPH]

Common Name

English

ETHOTOIN [VANDF]

Common Name

English

Ethotoin [WHO-DD]

Common Name

English

ETHOTOIN [ORANGE BOOK]

Common Name

English

ETHOTOIN [USP-RS]

Common Name

English

ACCENON

Brand Name

English

2,4-IMIDAZOLIDINEDIONE, 3-ETHYL-5-PHENYL-, (±)-

Systematic Name

English

Classification Tree Code System Code

WHO-ATC

N03AB01