Ethotoin

Ethotoin (previously marketed as Peganone) is an anticonvulsant drug used in the treatment of epilepsy.^[1] It is a hydantoin, similar to phenytoin. It is not available in the United States.

Ethotoin

Clinical data
AHFS/Drugs.com	Consumer Drug Information
MedlinePlus	a682022
Pregnancy category	C
Routes of administration	By mouth (tablets)
ATC code	N03AB01 (WHO)
Pharmacokinetic data
Elimination half-life	3–9 hours
Identifiers
IUPAC name 3-Ethyl-5-phenyl-imidazolidine-2,4-dione
CAS Number	86-35-1^Y
PubChem CID	3292
IUPHAR/BPS	7183
DrugBank	DB00754^Y
ChemSpider	3176^Y
UNII	46QG38NC4U
KEGG	D00708^Y
ChEBI	CHEBI:4888^Y
ChEMBL	ChEMBL1095^Y
CompTox Dashboard (EPA)	DTXSID6023020
ECHA InfoCard	100.001.514
Chemical and physical data
Formula	C11H12N2O2
Molar mass	204.229 g·mol^−1
3D model (JSmol)	Interactive image
SMILES O=C2NC(c1ccccc1)C(=O)N2CC
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)^Y Key:SZQIFWWUIBRPBZ-UHFFFAOYSA-N^Y
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Mechanism of action

The mechanism of action of ethotoin is similar to that of phenytoin.^{[citation needed]}

Approval history

• 1957 Peganone was granted Food and Drug Administration (FDA) approval to Abbott Laboratories for treatment of grand mal (tonic clonic) and partial complex (psychomotor) seizures.
• 2003 Peganone was acquired from Abbott Laboratories by Ovation Pharmaceuticals (specialty pharmaceutical company who acquire underpromoted branded pharmaceutical products).
• 2018 It was announced by Recordati Rare Diseases Inc. that due to a combination of low product demand and complex manufacturing difficulties, product manufacturing, distribution and sale was being discontinued.

Indications and usage

Ethotoin is indicated for tonic-clonic and partial complex seizures.^[2]

Dosing

Ethotoin is available in 250 mg tablets.^[3][4] It is taken orally in 4 to 6 divided doses per day, preferably after food.

Side effects

Side effects include ataxia, visual disturbances, rash, and gastrointestinal problems.^{[citation needed]}

Chemistry

Ethotoin is synthesized by the reaction of benzaldehyde oxynitrile (2) with urea or ammonium bicarbonate, which forms an intermediate urea derivative (3) which on acidic conditions cyclizes to 5-phenylhydantoin (4).^[5] Alkylation of this product using ethyl iodide leads to the formation of ethotoin (5).

 

Synthesis of ethotoin

References

1. Schwade ED, Richards RK, Everett GM (May 1956). "Peganone, a new antiepileptic drug". Dis Nerv Syst. 17 (5): 155–8. PMID 13317788.
2. Shorvon, S.D.; Fish, David R.; Perucca, Emilio; Dodson, W. Edwin, eds. (2004). The Treatment of Epilepsy. Blackwell Publishing. ISBN 0-632-06046-8.
3. "Ethotoin". drugs.com.
4. "PEGANONE 250 mg Ethotoin Tablets, USP" (PDF).
5. A. Pinner, Chem. Ber., 21, 2324 (1888); W.J. Close, U.S. patent 2,793,157 (1946)