MEPHENYTOIN

Details

Stereochemistry	RACEMIC
Molecular Formula	C12H14N2O2
Molecular Weight	218.2518
Optical Activity	( + / - )
Defined Stereocenters	0 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCC1(NC(=O)N(C)C1=O)C2=CC=CC=C2

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
Sources: http://www.drugbank.ca/drugs/DB00532
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.

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/DB00532	Inhibitor 8228

Conditions

Condition	Modality	Targets	Highest Phase	Product
Epilepsy 122 Sources: https://www.drugs.com/pro/mesantoin.html	Primary		Approved 8360	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

Dose	Population	Adverse events
7200 mg single, oral Overdose Dose: 7200 mg Route: oral Route: single Dose: 7200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11192466	unknown, 17 years n = 1 Health Status: unknown Age Group: 17 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/11192466	Other AEs: Stupor... Other AEs: Stupor Sources: https://pubmed.ncbi.nlm.nih.gov/11192466
12000 mg single, oral Overdose Dose: 12000 mg Route: oral Route: single Dose: 12000 mg Co-administed with:: valproic acid Sources: https://pubmed.ncbi.nlm.nih.gov/11192466	unknown, 26 years n = 1 Health Status: unknown Age Group: 26 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/11192466	Other AEs: Coma... Other AEs: Coma Sources: https://pubmed.ncbi.nlm.nih.gov/11192466
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: https://pubmed.ncbi.nlm.nih.gov/18135085	unhealthy, 31 years n = 1 Health Status: unhealthy Condition: epileptic attacks Age Group: 31 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18135085	Disc. AE: Pancytopenia... AEs leading to discontinuation/dose reduction: Pancytopenia (grade 5, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/18135085
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: https://pubmed.ncbi.nlm.nih.gov/1001284	unhealthy, adult n = 22 Health Status: unhealthy Condition: Seizure Age Group: adult Sex: M+F Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/1001284	Disc. AE: Aplastic anemia... AEs leading to discontinuation/dose reduction: Aplastic anemia (grade 5, 1 patient) Sources: https://pubmed.ncbi.nlm.nih.gov/1001284

AEs

AE	Significance	Dose	Population
Stupor		7200 mg single, oral Overdose Dose: 7200 mg Route: oral Route: single Dose: 7200 mg Sources: https://pubmed.ncbi.nlm.nih.gov/11192466	unknown, 17 years n = 1 Health Status: unknown Age Group: 17 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/11192466
Coma		12000 mg single, oral Overdose Dose: 12000 mg Route: oral Route: single Dose: 12000 mg Co-administed with:: valproic acid Sources: https://pubmed.ncbi.nlm.nih.gov/11192466	unknown, 26 years n = 1 Health Status: unknown Age Group: 26 years Sex: F Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/11192466
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: https://pubmed.ncbi.nlm.nih.gov/18135085	unhealthy, 31 years n = 1 Health Status: unhealthy Condition: epileptic attacks Age Group: 31 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/18135085
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: https://pubmed.ncbi.nlm.nih.gov/1001284	unhealthy, adult n = 22 Health Status: unhealthy Condition: Seizure Age Group: adult Sex: M+F Population Size: 22 Sources: https://pubmed.ncbi.nlm.nih.gov/1001284

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
	substrate 1010

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 985 CYP3A 189

Drug as victim

Target	Modality	Activity
CYP2C9 1010	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/11329260/	no
CYP2C19 985	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/30124163/; https://pubmed.ncbi.nlm.nih.gov/25904760/	yes
CYP3A 189	substrate 3326 Sources: https://pubmed.ncbi.nlm.nih.gov/15499174/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:6757	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:6757
ChemicalBook	CB0225135	https://www.chemicalbook.com/ChemicalProductProperty_EN_CB0225135
MolPort	MolPort-003-666-498	https://www.molport.com/shop/molecule-link/MolPort-003-666-498
eMolecules	731057	https://www.emolecules.com/cgi-bin/more?vid=731057

PubMed

Title	Date	PubMed
In vitro inhibitory effect of 1-aminobenzotriazole on drug oxidations catalyzed by human cytochrome P450 enzymes: a comparison with SKF-525A and ketoconazole.	2003	15618748
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	12900870
Identification of the human cytochrome P450s responsible for the in vitro metabolism of a leukotriene B4 receptor antagonist, CP-195,543.	2003 Dec	14742142
Hepatic CYP2B6 expression: gender and ethnic differences and relationship to CYP2B6 genotype and CAR (constitutive androstane receptor) expression.	2003 Dec	14551287
Artemisinin autoinduction is caused by involvement of cytochrome P450 2B6 but not 2C9.	2003 Jul	12844133
Cytochrome P450 inhibition using recombinant proteins and mass spectrometry/multiple reaction monitoring technology in a cassette incubation.	2003 Jul	12814974
Metabolism of citalopram enantiomers in CYP2C19/CYP2D6 phenotyped panels of healthy Swedes.	2003 Oct	12968986
Interferon-beta treatment in patients with multiple sclerosis does not alter CYP2C19 or CYP2D6 activity.	2003 Sep	12919185
Quantification of mephenytoin and its metabolites 4'-hydroxymephenytoin and nirvanol in human urine using a simple sample processing method.	2004	15282764
Ethnic differences in genetic polymorphisms of CYP2D6, CYP2C19, CYP3As and MDR1/ABCB1.	2004 Apr	15499174
Key structural features of ligands for activation of human pregnane X receptor.	2004 Apr	15039302
Inhibition of cytochrome P450 activities by oleanolic acid and ursolic acid in human liver microsomes.	2004 Apr 16	15043991
Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities.	2004 Aug	15258107
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	15648259
Bioequivalence revisited: influence of age and sex on CYP enzymes.	2004 Dec	15592333
Inhibitory effects of the monoamine oxidase inhibitor tranylcypromine on the cytochrome P450 enzymes CYP2C19, CYP2C9, and CYP2D6.	2004 Feb	15049511
Assessment of drug-drug interaction potential of enfuvirtide in human immunodeficiency virus type 1-infected patients.	2004 Jun	15179410
Validated assays for human cytochrome P450 activities.	2004 Jun	15155557
Selective inhibition of CYP2B6-catalyzed bupropion hydroxylation in human liver microsomes in vitro.	2004 Jun	15155554
Omeprazole as a CYP2C19 marker in Chinese subjects: assessment of its gene-dose effect and intrasubject variability.	2004 Jun	15145965
The influence of St John's Wort on CYP2C19 activity with respect to genotype.	2004 Jun	15145964
Developmental expression of human hepatic CYP2C9 and CYP2C19.	2004 Mar	14634042
Potential of pranlukast and zafirlukast in the inhibition of human liver cytochrome P450 enzymes.	2004 May	15370959
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	15370958
Metabolism of human cytochrome P450 marker substrates in mouse: a strain and gender comparison.	2004 Sep	15742976
CYP2B6, CYP3A4, and CYP2C19 are responsible for the in vitro N-demethylation of meperidine in human liver microsomes.	2004 Sep	15319333
Active-site characteristics of CYP2C19 and CYP2C9 probed with hydantoin and barbiturate inhibitors.	2004 Sep 1	15288804
High-throughput screening of inhibitory potential of nine cytochrome P450 enzymes in vitro using liquid chromatography/tandem mass spectrometry.	2005	16124035
Lack of interaction of milnacipran with the cytochrome p450 isoenzymes frequently involved in the metabolism of antidepressants.	2005	16122284
Polymorphism of CYP2D6, CYP2C19, CYP2C9 and CYP2C8 in the Faroese population.	2005 Aug	16025294
Automated screening with confirmation of mechanism-based inactivation of CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2 in pooled human liver microsomes.	2005 Aug	15860655
Effect of propiverine on cytochrome P450 enzymes: a cocktail interaction study in healthy volunteers.	2005 Dec	16183781
Effect of age and postoperative time on cytochrome p450 enzyme activity following liver transplantation.	2005 Jun	15901748
Cytochrome P-450 activity is differentially altered in severely injured patients.	2005 Mar	15753745
Automated assessment of time-dependent inhibition of human cytochrome P450 enzymes using liquid chromatography-tandem mass spectrometry analysis.	2005 Nov	16049126
CYP2C19-mediated (S)-mephenytoin 4'-hydroxylation assayed by high-performance liquid chromatography with radiometric detection.	2006	16719381
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	16395737
Investigation of sarizotan's impact on the pharmacokinetics of probe drugs for major cytochrome P450 isoenzymes: a combined cocktail trial.	2006 Apr	16525816
CYP2C76, a novel cytochrome P450 in cynomolgus monkey, is a major CYP2C in liver, metabolizing tolbutamide and testosterone.	2006 Aug	16648389
In vitro metabolism of tributyltin and triphenyltin by human cytochrome P-450 isoforms.	2006 Dec 7	16978758
A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants.	2006 Jan	16413245
Cynomolgus monkey cytochrome P450 2C43: cDNA cloning, heterologous expression, purification and characterization.	2006 May	16751594
Effect of conjugated equine estrogens on oxidative metabolism in middle-aged and elderly postmenopausal women.	2006 Nov	17050794
The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes.	2006 Nov 25	16978661
Evaluation of the activity of CYP2C19 in Gujrati and Marwadi subjects living in Mumbai (Bombay).	2006 Oct 24	17062149
Validation of incorporating flurbiprofen into the Pittsburgh cocktail.	2006 Sep	16952492
Liver disease selectively modulates cytochrome P450--mediated metabolism.	2006 Sep	16952490
Effects of individual ginsenosides, ginkgolides and flavonoids on CYP2C19 and CYP2D6 activity in human liver microsomes.	2006 Sep	16922812
Appropriate phenotyping procedures for drug metabolizing enzymes and transporters in humans and their simultaneous use in the "cocktail" approach.	2007 Feb	17259951
CYP2C76-mediated species difference in drug metabolism: a comparison of pitavastatin metabolism between monkeys and humans.	2007 Jan	17178632

Patents

Sample Use Guides

In Vivo Use Guide

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

Official Name

English

mephenytoin [INN]

Common Name

English

NSC-34652

Code

English

ETHYLMETHYLHYDANTOIN

Systematic Name

English

(±)-5-ETHYL-3-METHYL-5-PHENYLHYDANTOIN

Systematic Name

English

Mephenytoin [WHO-DD]

Common Name

English

MESANTOIN

Brand Name

English

PHENYLETHYLMETHYLHYDANTOIN

Systematic Name

English

MEPHENYTOIN [VANDF]

Common Name

English

MEPHENYTOIN [ORANGE BOOK]

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

MEPHENYTOIN [USP IMPURITY]

Common Name

English

Classification Tree Code System Code

NCI_THESAURUS

C264