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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:: Description was created based on several sources, including 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

-7.3198082E11
Doses

Doses

DosePopulationAdverse events​
7200 mg single, oral
Overdose
Dose: 7200 mg
Route: oral
Route: single
Dose: 7200 mg
Sources:
unknown, 17 years
n = 1
Health Status: unknown
Age Group: 17 years
Sex: M
Population Size: 1
Sources:
Other AEs: Stupor...
12000 mg single, oral
Overdose
Dose: 12000 mg
Route: oral
Route: single
Dose: 12000 mg
Co-administed with::
valproic acid
Sources:
unknown, 26 years
n = 1
Health Status: unknown
Age Group: 26 years
Sex: F
Population Size: 1
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
Co-administed with::
phenobarbital(oral; 6 months)
Sources:
unhealthy, 31 years
n = 1
Health Status: unhealthy
Condition: epileptic attacks
Age Group: 31 years
Sex: M
Population Size: 1
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
n = 22
Health Status: unhealthy
Condition: Seizure
Age Group: adult
Sex: M+F
Population Size: 22
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
n = 1
Health Status: unknown
Age Group: 17 years
Sex: M
Population Size: 1
Sources:
Coma
12000 mg single, oral
Overdose
Dose: 12000 mg
Route: oral
Route: single
Dose: 12000 mg
Co-administed with::
valproic acid
Sources:
unknown, 26 years
n = 1
Health Status: unknown
Age Group: 26 years
Sex: F
Population Size: 1
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
Co-administed with::
phenobarbital(oral; 6 months)
Sources:
unhealthy, 31 years
n = 1
Health Status: unhealthy
Condition: epileptic attacks
Age Group: 31 years
Sex: M
Population Size: 1
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
n = 22
Health Status: unhealthy
Condition: Seizure
Age Group: adult
Sex: M+F
Population Size: 22
Sources:
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer


Drug as victim
PubMed

PubMed

TitleDatePubMed
In vitro inhibitory effect of 1-aminobenzotriazole on drug oxidations catalyzed by human cytochrome P450 enzymes: a comparison with SKF-525A and ketoconazole.
2003
Capillary electrophoresis to assess drug metabolism induced in vitro using single CYP450 enzymes (Supersomes): application to the chiral metabolism of mephenytoin and methadone.
2003 Aug
Identification of the human cytochrome P450s responsible for the in vitro metabolism of a leukotriene B4 receptor antagonist, CP-195,543.
2003 Dec
Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression.
2003 Dec
Artemisinin autoinduction is caused by involvement of cytochrome P450 2B6 but not 2C9.
2003 Jul
Cytochrome P450 inhibition using recombinant proteins and mass spectrometry/multiple reaction monitoring technology in a cassette incubation.
2003 Jul
Metabolism of citalopram enantiomers in CYP2C19/CYP2D6 phenotyped panels of healthy Swedes.
2003 Oct
Interferon-beta treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity.
2003 Sep
Quantification of mephenytoin and its metabolites 4'-hydroxymephenytoin and nirvanol in human urine using a simple sample processing method.
2004
Ethnic differences in genetic polymorphisms of CYP2D6, CYP2C19, CYP3As and MDR1/ABCB1.
2004 Apr
Key structural features of ligands for activation of human pregnane X receptor.
2004 Apr
Inhibition of cytochrome P450 activities by oleanolic acid and ursolic acid in human liver microsomes.
2004 Apr 16
Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities.
2004 Aug
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
Assessment of drug-drug interaction potential of enfuvirtide in human immunodeficiency virus type 1-infected patients.
2004 Jun
Validated assays for human cytochrome P450 activities.
2004 Jun
Selective inhibition of CYP2B6-catalyzed bupropion hydroxylation in human liver microsomes in vitro.
2004 Jun
Omeprazole as a CYP2C19 marker in Chinese subjects: assessment of its gene-dose effect and intrasubject variability.
2004 Jun
The influence of St John's Wort on CYP2C19 activity with respect to genotype.
2004 Jun
Developmental expression of human hepatic CYP2C9 and CYP2C19.
2004 Mar
Potential of pranlukast and zafirlukast in the inhibition of human liver cytochrome P450 enzymes.
2004 May
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
Metabolism of human cytochrome P450 marker substrates in mouse: a strain and gender comparison.
2004 Sep
CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes.
2004 Sep
Active-site characteristics of CYP2C19 and CYP2C9 probed with hydantoin and barbiturate inhibitors.
2004 Sep 1
High-throughput screening of inhibitory potential of nine cytochrome P450 enzymes in vitro using liquid chromatography/tandem mass spectrometry.
2005
Lack of interaction of milnacipran with the cytochrome p450 isoenzymes frequently involved in the metabolism of antidepressants.
2005
Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population.
2005 Aug
Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes.
2005 Aug
Effect of propiverine on cytochrome P450 enzymes: a cocktail interaction study in healthy volunteers.
2005 Dec
Effect of age and postoperative time on cytochrome p450 enzyme activity following liver transplantation.
2005 Jun
Cytochrome P-450 activity is differentially altered in severely injured patients.
2005 Mar
Automated assessment of time-dependent inhibition of human cytochrome P450 enzymes using liquid chromatography-tandem mass spectrometry analysis.
2005 Nov
CYP2C19-mediated (S)-mephenytoin 4'-hydroxylation assayed by high-performance liquid chromatography with radiometric detection.
2006
Enantiospecific separation and quantitation of mephenytoin and its metabolites nirvanol and 4'-hydroxymephenytoin in human plasma and urine by liquid chromatography/tandem mass spectrometry.
2006
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
In vitro metabolism of tributyltin and triphenyltin by human cytochrome P-450 isoforms.
2006 Dec 7
A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants.
2006 Jan
Cynomolgus monkey cytochrome P450 2C43: cDNA cloning, heterologous expression, purification and characterization.
2006 May
Effect of conjugated equine estrogens on oxidative metabolism in middle-aged and elderly postmenopausal women.
2006 Nov
The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes.
2006 Nov 25
Evaluation of the activity of CYP2C19 in Gujrati and Marwadi subjects living in Mumbai (Bombay).
2006 Oct 24
Validation of incorporating flurbiprofen into the Pittsburgh cocktail.
2006 Sep
Liver disease selectively modulates cytochrome P450--mediated metabolism.
2006 Sep
Effects of individual ginsenosides, ginkgolides and flavonoids on CYP2C19 and CYP2D6 activity in human liver microsomes.
2006 Sep
Appropriate phenotyping procedures for drug metabolizing enzymes and transporters in humans and their simultaneous use in the "cocktail" approach.
2007 Feb
CYP2C76-mediated species difference in drug metabolism: a comparison of pitavastatin metabolism between monkeys and humans.
2007 Jan
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
In Vitro Use Guide
Unknown
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