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 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Epilepsy 121 Sources: https://www.drugs.com/pro/mesantoin.html	Primary		Approved 8429	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 1946

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 1037

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
	CYP2C19 991 CYP3A 191

Drug as victim

Target	Modality	Activity
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/11329260/	no
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/30124163/; https://pubmed.ncbi.nlm.nih.gov/25904760/	yes
CYP3A 191	substrate 3367 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
Mephenytoin: a reappraisal.	1976 Dec	1001284
Fluoxetine pharmacokinetics and effect on CYP2C19 in young and elderly volunteers.	2001 Apr	11270912
The prevalence of CYP2D6 and CYP2C19 genotypes in a population of healthy Dutch volunteers.	2001 Dec	11829201
Phenotype analysis of cytochrome P450 2C19 in Chinese subjects with mephenytoin S/R enantiomeric ratio in urine measured by chiral GC.	2001 Feb	11180294
Stereoselective pharmacokinetics of pantoprazole, a proton pump inhibitor, in extensive and poor metabolizers of S-mephenytoin.	2001 Mar	11240974
Metabolic characterization of the major human small intestinal cytochrome p450s.	2001 Mar	11181505
An interaction between the cytochrome P450 probe substrates chlorzoxazone (CYP2E1) and midazolam (CYP3A).	2001 Nov	11736864
Acute hypoxia and cytochrome P450-mediated hepatic drug metabolism in humans.	2002 Apr	11956503
Amino acid residues affecting the activities of human cytochrome P450 2C9 and 2C19.	2002 Aug	12124312
Effect of chronic disulfiram administration on the activities of CYP1A2, CYP2C19, CYP2D6, CYP2E1, and N-acetyltransferase in healthy human subjects.	2002 Feb	11851639
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	12142727
Effect of growth hormone on hepatic cytochrome P450 activity in healthy elderly men.	2002 Mar	11907490
(+)-N-3-Benzyl-nirvanol and (-)-N-3-benzyl-phenobarbital: new potent and selective in vitro inhibitors of CYP2C19.	2002 Mar	11854139
Substrate specificity for rat cytochrome P450 (CYP) isoforms: screening with cDNA-expressed systems of the rat.	2002 Mar 1	11911841
Plasma levels of TNF-alpha and IL-6 are inversely related to cytochrome P450-dependent drug metabolism in patients with congestive heart failure.	2002 Oct	12411982
Essential requirements for substrate binding affinity and selectivity toward human CYP2 family enzymes.	2003 Jan 1	12464242
Artemisinin autoinduction is caused by involvement of cytochrome P450 2B6 but not 2C9.	2003 Jul	12844133
mRNA and protein expression of dog liver cytochromes P450 in relation to the metabolism of human CYP2C substrates.	2003 Mar	12637241
Quantification of mephenytoin and its metabolites 4'-hydroxymephenytoin and nirvanol in human urine using a simple sample processing method.	2004	15282764
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
Assessment of drug-drug interaction potential of enfuvirtide in human immunodeficiency virus type 1-infected patients.	2004 Jun	15179410
Selective inhibition of CYP2B6-catalyzed bupropion hydroxylation in human liver microsomes in vitro.	2004 Jun	15155554
The influence of St John's Wort on CYP2C19 activity with respect to genotype.	2004 Jun	15145964
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
Cytochrome P-450 activity is differentially altered in severely injured patients.	2005 Mar	15753745
The inhibitory effect of polyunsaturated fatty acids on human CYP enzymes.	2006 Nov 25	16978661
Validation of incorporating flurbiprofen into the Pittsburgh cocktail.	2006 Sep	16952492

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

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WHO-ATC

N03AB54

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NDF-RT

N0000008486

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WHO-VATC

QN03AB54

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WHO-ATC

N03AB04

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WHO-VATC

QN03AB04

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NDF-RT

N0000175753

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Code System Code Type Description

RXCUI

6757

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RxNorm

ChEMBL

CHEMBL861

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PUBCHEM

4060

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WIKIPEDIA

MEPHENYTOIN

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IUPHAR

7223

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EVMPD

SUB08749MIG

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DRUG BANK

DB00532

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EPA CompTox

DTXSID9023257

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MERCK INDEX

m7190

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Merck Index

HSDB

3581

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CAS

50-12-4

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MESH

D008617

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FDA UNII

R420KW629U

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NSC

34652

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CHEBI

6757

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INN

1463

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ECHA (EC/EINECS)

200-012-8

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SMS_ID

100000081496

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NCI_THESAURUS

C66091

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DRUG CENTRAL

1695

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ACTIVE MOIETY


					R420KW629U

MEPHENYTOIN

SALT/SOLVATE (PARENT)


					TYD93VML2K

MEPHENYTOIN SODIUM

Details

SMILES

InChI

DescriptionSources: http://www.drugbank.ca/drugs/DB00532Curator's Comment: Description was created based on several sources, including https://www.drugs.com/mtm/mephenytoin.html

CNS Activity

Originator

Approval Year

Targets

Conditions

Approved Use

Launch Date

Doses

AEs

Overview

OverviewOther

Drug as victim

Sourcing

PubMed

Patents

Sample Use Guides

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