U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry RACEMIC
Molecular Formula C12H14N2O2
Molecular Weight 218.2522
Optical Activity ( + / - )
Defined Stereocenters 0 / 1
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MEPHENYTOIN

SMILES

CCC1(c2ccccc2)C(=O)N(C)C(=N1)O

InChI

InChIKey=GMHKMTDVRCWUDX-UHFFFAOYSA-N
InChI=1S/C12H14N2O2/c1-3-12(9-7-5-4-6-8-9)10(15)14(2)11(16)13-12/h4-8H,3H2,1-2H3,(H,13,16)

HIDE SMILES / InChI

Description
Curator's Comment:: https://www.drugs.com/mtm/mephenytoin.html

Mephenytoin is an antiepileptic drug which can be useful in the treatment of epilepsy. The primary site of action appears to be the motor cortex where spread of seizure activity is inhibited. Possibly by promoting sodium efflux from neurons, mephenytoin tends to stabilize the threshold against hyperexcitability caused by excessive stimulation or environmental changes capable of reducing membrane sodium gradient. This includes the reduction of posttetanic potentiation at synapses. Loss of posttetanic potentiation prevents cortical seizure foci from detonating adjacent cortical areas. Mephenytoin reduces the maximal activity of brain stem centers responsible for the tonic phase of tonic-clonic (grand mal) seizures. The mechanism of action of mephenytoin is not definitely known, but extensive research strongly suggests that its main mechanism is to block frequency-, use- and voltage-dependent neuronal sodium channels, and therefore limit repetitive firing of action potentials. Mephenytoin is no longer available in the US or the UK. It is still studied largely because of its interesting hydroxylation polymorphism.

Originator

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Mesantoin

Approved Use

For the control of grand mal, focal, Jacksonian, and psychomotor seizures in those patients who have been refractory to less toxic anticonvulsants.

Launch Date

-731980800000
Doses

Doses

DosePopulationAdverse events​
7200 mg single, oral
Overdose
Dose: 7200 mg
Route: oral
Route: single
Dose: 7200 mg
Sources:
unknown, 17 years
Health Status: unknown
Age Group: 17 years
Sex: M
Sources:
Other AEs: Stupor...
12000 mg single, oral
Overdose
Dose: 12000 mg
Route: oral
Route: single
Dose: 12000 mg
Sources:
unknown, 26 years
Health Status: unknown
Age Group: 26 years
Sex: F
Sources:
Other AEs: Coma...
0.1 g 1 times / day multiple, oral
Dose: 0.1 g, 1 times / day
Route: oral
Route: multiple
Dose: 0.1 g, 1 times / day
Sources:
unhealthy, 31 years
Health Status: unhealthy
Age Group: 31 years
Sex: M
Sources:
Disc. AE: Pancytopenia...
AEs leading to
discontinuation/dose reduction:
Pancytopenia (grade 5, 1 patient)
Sources:
6.8 mg/kg 1 times / day multiple, oral
Dose: 6.8 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 6.8 mg/kg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Disc. AE: Aplastic anemia...
AEs leading to
discontinuation/dose reduction:
Aplastic anemia (grade 5, 1 patient)
Sources:
AEs

AEs

AESignificanceDosePopulation
Stupor
7200 mg single, oral
Overdose
Dose: 7200 mg
Route: oral
Route: single
Dose: 7200 mg
Sources:
unknown, 17 years
Health Status: unknown
Age Group: 17 years
Sex: M
Sources:
Coma
12000 mg single, oral
Overdose
Dose: 12000 mg
Route: oral
Route: single
Dose: 12000 mg
Sources:
unknown, 26 years
Health Status: unknown
Age Group: 26 years
Sex: F
Sources:
Pancytopenia grade 5, 1 patient
Disc. AE
0.1 g 1 times / day multiple, oral
Dose: 0.1 g, 1 times / day
Route: oral
Route: multiple
Dose: 0.1 g, 1 times / day
Sources:
unhealthy, 31 years
Health Status: unhealthy
Age Group: 31 years
Sex: M
Sources:
Aplastic anemia grade 5, 1 patient
Disc. AE
6.8 mg/kg 1 times / day multiple, oral
Dose: 6.8 mg/kg, 1 times / day
Route: oral
Route: multiple
Dose: 6.8 mg/kg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M+F
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victim
PubMed

PubMed

TitleDatePubMed
Phenotype analysis of cytochrome P450 2C19 in Chinese subjects with mephenytoin S/R enantiomeric ratio in urine measured by chiral GC.
2001 Feb
Pharmacokinetic drug interaction potential of risperidone with cytochrome p450 isozymes as assessed by the dextromethorphan, the caffeine, and the mephenytoin test.
2001 Jun
Mephenytoin as a probe for CYP2C19 phenotyping:effect of sample storage, intra-individual reproducibility and occurrence of adverse events.
2001 May
Identification and functional characterization of new potentially defective alleles of human CYP2C19.
2002 Dec
Carbamazepine and oxcarbazepine decrease phenytoin metabolism through inhibition of CYP2C19.
2002 Dec
The pharmacokinetics of ketobemidone are not affected by CYP2D6 or CYP2C19 phenotype.
2002 Feb
Evidence for environmental influence on CYP2D6-catalysed debrisoquine hydroxylation as demonstrated by phenotyping and genotyping of Ethiopians living in Ethiopia or in Sweden.
2002 Jul
Cytochrome P450 enzymes contributing to demethylation of maprotiline in man.
2002 Mar
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.
2003 Jan 1
Cytochrome P450 inhibition using recombinant proteins and mass spectrometry/multiple reaction monitoring technology in a cassette incubation.
2003 Jul
Verification of the selectivity of (+)N-3-benzylnirvanol as a CYP2C19 inhibitor.
2003 Mar
Interferon-beta treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity.
2003 Sep
Ethnic differences in genetic polymorphisms of CYP2D6, CYP2C19, CYP3As and MDR1/ABCB1.
2004 Apr
Inhibition of cytochrome P450 activities by oleanolic acid and ursolic acid in human liver microsomes.
2004 Apr 16
Studies of binding modes of (S)-mephenytoin to wild types and mutants of cytochrome P450 2C19 and 2C9 using homology modeling and computational docking.
2004 Dec
Bioequivalence revisited: influence of age and sex on CYP enzymes.
2004 Dec
Inhibitory effects of the monoamine oxidase inhibitor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C9, and CYP2D6.
2004 Feb
Identification and relative contributions of human cytochrome P450 isoforms involved in the metabolism of glibenclamide and lansoprazole: evaluation of an approach based on the in vitro substrate disappearance rate.
2004 May
Investigation of sarizotan's impact on the pharmacokinetics of probe drugs for major cytochrome P450 isoenzymes: a combined cocktail trial.
2006 Apr
CYP2C76, a novel cytochrome P450 in cynomolgus monkey, is a major CYP2C in liver, metabolizing tolbutamide and testosterone.
2006 Aug
Cynomolgus monkey cytochrome P450 2C43: cDNA cloning, heterologous expression, purification and characterization.
2006 May
The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes.
2006 Nov 25
Validation of incorporating flurbiprofen into the Pittsburgh cocktail.
2006 Sep
Patents

Sample Use Guides

The average dose of Mesantoin® (mephenytoin) for adults ranges from 2-6 tablets (0.2-0.6 Gm.) daily. In some instances it may be necessary to administer as much as 8 tablets or more daily in order to obtain full seizure control. Pediatric patients usually require from 1-4 tablets (0.1-0.4 Gm.) according to nature of seizures and age.
Route of Administration: Oral
Name Type Language
MEPHENYTOIN
HSDB   INN   MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   VANDF   WHO-DD  
USAN   INN  
Official Name English
MEPHENYTOIN [INN]
Common Name English
NSC-34652
Code English
ETHYLMETHYLHYDANTOIN
Systematic Name English
MEPHENYTOIN [USP]
Common Name English
(+/-)-5-ETHYL-3-METHYL-5-PHENYLHYDANTOIN
Systematic Name English
MESANTOIN
Brand Name English
PHENYLETHYLMETHYLHYDANTOIN
Systematic Name English
MEPHENYTOIN [VANDF]
Common Name English
MEPHENYTOIN [ORANGE BOOK]
Common Name English
MEPHENYTOIN [WHO-DD]
Common Name English
2,4-IMIDAZOLIDINEDIONE, 5-ETHYL-3-METHYL-5-PHENYL-, (+/-)-
Systematic Name English
MEPHENYTOIN [MI]
Common Name English
MEPHENYTOIN [MART.]
Common Name English
MEPHENYTOIN [USAN]
Common Name English
METHOIN
Common Name English
MEPHENYTOIN [HSDB]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C264
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
WHO-ATC N03AB54
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
NDF-RT N0000008486
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
WHO-VATC QN03AB54
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
WHO-ATC N03AB04
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
WHO-VATC QN03AB04
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
NDF-RT N0000175753
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
Code System Code Type Description
RXCUI
6757
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY RxNorm
ChEMBL
CHEMBL861
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
PUBCHEM
4060
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
WIKIPEDIA
MEPHENYTOIN
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
IUPHAR
7223
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
EVMPD
SUB08749MIG
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
DRUG BANK
DB00532
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
EPA CompTox
50-12-4
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
MERCK INDEX
M7190
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY Merck Index
HSDB
3581
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
CAS
50-12-4
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
MESH
D008617
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
FDA UNII
R420KW629U
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
INN
1463
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
ECHA (EC/EINECS)
200-012-8
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
NCI_THESAURUS
C66091
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY
DRUG CENTRAL
1695
Created by admin on Sat Jun 26 12:39:21 UTC 2021 , Edited by admin on Sat Jun 26 12:39:21 UTC 2021
PRIMARY