Identification
- Summary
Mephenytoin is a phenylhydantoin used to treat refractory partial epilepsy.
- Generic Name
- Mephenytoin
- DrugBank Accession Number
- DB00532
- Background
Mephenytoin is used for the treatment of refractory partial epilepsy. Mephenytoin is a solid. This compound belongs to the phenylhydantoins. These are heterocyclic aromatic compounds containing an imiazolidinedione moiety substituted by a phenyl group. Mephenytoin is known to target sodium channel protein type 5 subunit alpha. Cytochrome P450 2C19, Cytochrome P450 2C8, Cytochrome P450 2C9, Cytochrome P450 2B6, Cytochrome P450 1A2, and Cytochrome P450 2D6 are known to metabolize mephenytoin. Mephenytoin is a hydantoin-derivative anticonvulsant used to control various partial seizures. Mephenytoin and oxazolidinedione derivatives are associated with higher incidences of blood dyscrasias compared to other anticonvulsants.
- Type
- Small Molecule
- Groups
- Approved, Investigational, Withdrawn
- Structure
Structure for Mephenytoin (DB00532)
- Weight
- Average: 218.2518
Monoisotopic: 218.105527702 - Chemical Formula
- C12H14N2O2
- Synonyms
- mefenitoína
- Mephenytoin
Pharmacology
- Indication
For the treatment of refractory partial epilepsy.
Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.- Contraindications & Blackbox Warnings
Prevent Adverse Drug Events TodayTap into our Clinical API for life-saving information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events with our Clinical API- Pharmacodynamics
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.
- Mechanism of action
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.
Target Actions Organism ASodium channel protein type 5 subunit alpha inhibitorHumans UNuclear receptor subfamily 1 group I member 2 activatorHumans - Absorption
Not Available
- Volume of distribution
- 1.4 L/kg
- Protein binding
Not Available
- Metabolism
Hover over products below to view reaction partners
- Route of elimination
Not Available
- Half-life
Approximately 7 hours
- Clearance
Not Available
- Adverse Effects
Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
Interacting Gene/Enzyme Allele name Genotype(s) Defining Change(s) Type(s) Description Details Cytochrome P450 2C19 CYP2C19*3 (A;A) A Allele, homozygote Effect Directly Studied Patients with this genotype have reduced metabolism of mephenytoin. Details Cytochrome P450 2C19 CYP2C19*8 (C;C) / (C;T) T > C Effect Directly Studied Patients with this genotype have reduced metabolism of mephenytoin. Details Cytochrome P450 2C19 CYP2C19*7 (A;A) / (A;T) T > A Effect Directly Studied Patients with this genotype have reduced metabolism of mephenytoin. Details Cytochrome P450 2C19 CYP2C19*2A Not Available 681G>A Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*2B Not Available 681G>A Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*4 Not Available 1A>G Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*5 Not Available 1297C>T Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*6 Not Available 395G>A Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*7 Not Available 19294T>A Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*22 Not Available 557G>C / 991A>G Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*24 Not Available 99C>T / 991A>G … show all Effect Inferred Poor metabolizer, lower dose requirement Details Cytochrome P450 2C19 CYP2C19*35 Not Available 12662A>G Effect Inferred Poor metabolizer, lower dose requirement Details
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Integrate drug-drug
interactions in your software1,2-Benzodiazepine The risk or severity of CNS depression can be increased when Mephenytoin is combined with 1,2-Benzodiazepine. Abametapir The serum concentration of Mephenytoin can be increased when it is combined with Abametapir. Abatacept The metabolism of Mephenytoin can be increased when combined with Abatacept. Abiraterone The serum concentration of Mephenytoin can be increased when it is combined with Abiraterone. Abrocitinib The metabolism of Abrocitinib can be decreased when combined with Mephenytoin. - Food Interactions
- Not Available
Products
Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Mesantoin Tablet 100 mg/1 Oral Novartis 1946-10-23 2010-08-10 US 
Categories
- ATC Codes
- N03AB04 — MephenytoinN03AB54 — Mephenytoin, combinations
- Drug Categories
- Anti-epileptic Agent
- Anticonvulsants
- Central Nervous System Agents
- Central Nervous System Depressants
- Cytochrome P-450 CYP1A2 Substrates
- Cytochrome P-450 CYP2B6 Substrates
- Cytochrome P-450 CYP2C19 Inhibitors
- Cytochrome P-450 CYP2C19 inhibitors (strength unknown)
- Cytochrome P-450 CYP2C19 Substrates
- Cytochrome P-450 CYP2C8 Substrates
- Cytochrome P-450 CYP2C9 Substrates
- Cytochrome P-450 CYP2D6 Substrates
- Cytochrome P-450 Enzyme Inhibitors
- Cytochrome P-450 Substrates
- Decreased Central Nervous System Disorganized Electrical Activity
- Hydantoins
- Imidazoles
- Imidazolidines
- Nervous System
- Thyroxine-binding globulin substrates
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as phenylhydantoins. These are heterocyclic aromatic compounds containing an imiazolidinedione moiety substituted by a phenyl group.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Azolidines
- Sub Class
- Imidazolidines
- Direct Parent
- Phenylhydantoins
- Alternative Parents
- Phenylimidazolidines / Alpha amino acids and derivatives / N-acyl ureas / Benzene and substituted derivatives / Dicarboximides / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives show 1 more
- Substituents
- 5-phenylhydantoin / Alpha-amino acid or derivatives / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbonic acid derivative / Carbonyl group / Carboxylic acid derivative / Dicarboximide / Hydrocarbon derivative show 11 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Humans and other mammals
Chemical Identifiers
- UNII
- R420KW629U
- CAS number
- 50-12-4
- InChI Key
- GMHKMTDVRCWUDX-UHFFFAOYSA-N
- InChI
- 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)
- IUPAC Name
- 5-ethyl-3-methyl-5-phenylimidazolidine-2,4-dione
- SMILES
- CCC1(NC(=O)N(C)C1=O)C1=CC=CC=C1
References
- General References
- Not Available
- External Links
- Human Metabolome Database
- HMDB0014673
- KEGG Drug
- D00375
- PubChem Compound
- 4060
- PubChem Substance
- 46508677
- ChemSpider
- 3920
- BindingDB
- 50103593
- 6757
- ChEBI
- 6757
- ChEMBL
- CHEMBL861
- Therapeutic Targets Database
- DAP000508
- PharmGKB
- PA450373
- Drugs.com
- Drugs.com Drug Page
- Wikipedia
- Mephenytoin
- MSDS
- Download (73.1 KB)
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count Not Available Unknown Status Other Healthy Subjects (HS) 1
Pharmacoeconomics
- Manufacturers
- Novartis pharmaceuticals corp
- Packagers
- Physicians Total Care Inc.
- Dosage Forms
Form Route Strength Tablet Oral 100 mg/1 - Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
Property Value Source melting point (°C) 135 °C PhysProp water solubility 1270 mg/L Not Available logP 1.69 SANGSTER (1994) pKa 8.51 TOMLINSON,E & HAFKENSCHEID,TL (1986) - Predicted Properties
Property Value Source Water Solubility 0.97 mg/mL ALOGPS logP 1.64 ALOGPS logP 1.67 Chemaxon logS -2.4 ALOGPS pKa (Strongest Acidic) 11.09 Chemaxon pKa (Strongest Basic) -8.1 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 2 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 49.41 Å2 Chemaxon Rotatable Bond Count 2 Chemaxon Refractivity 59.54 m3·mol-1 Chemaxon Polarizability 22.67 Å3 Chemaxon Number of Rings 2 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9771 Caco-2 permeable + 0.6007 P-glycoprotein substrate Non-substrate 0.5353 P-glycoprotein inhibitor I Non-inhibitor 0.8782 P-glycoprotein inhibitor II Non-inhibitor 0.8593 Renal organic cation transporter Non-inhibitor 0.9017 CYP450 2C9 substrate Non-substrate 0.7827 CYP450 2D6 substrate Non-substrate 0.9117 CYP450 3A4 substrate Non-substrate 0.6645 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9232 CYP450 2C19 inhibitor Non-inhibitor 0.9026 CYP450 3A4 inhibitor Non-inhibitor 0.8812 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9185 Ames test Non AMES toxic 0.8301 Carcinogenicity Non-carcinogens 0.7739 Biodegradation Not ready biodegradable 0.9654 Rat acute toxicity 2.3788 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9518 hERG inhibition (predictor II) Non-inhibitor 0.8827
Spectra
- Mass Spec (NIST)
- Download (8.17 KB)
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 156.0324268 predictedDarkChem Lite v0.1.0 [M-H]- 152.1886 predictedDeepCCS 1.0 (2019) [M+H]+ 157.0989268 predictedDarkChem Lite v0.1.0 [M+H]+ 154.54659 predictedDeepCCS 1.0 (2019) [M+Na]+ 156.4676268 predictedDarkChem Lite v0.1.0 [M+Na]+ 160.63972 predictedDeepCCS 1.0 (2019)
Targets
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- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Inhibitor
- General Function
- Voltage-gated sodium channel activity involved in sa node cell action potential
- Specific Function
- This protein mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the pr...
- Gene Name
- SCN5A
- Uniprot ID
- Q14524
- Uniprot Name
- Sodium channel protein type 5 subunit alpha
- Molecular Weight
- 226937.475 Da
References
- Lenkowski PW, Ko SH, Anderson JD, Brown ML, Patel MK: Block of human NaV1.5 sodium channels by novel alpha-hydroxyphenylamide analogues of phenytoin. Eur J Pharm Sci. 2004 Apr;21(5):635-44. [Article]
- Swadron SP, Rudis MI, Azimian K, Beringer P, Fort D, Orlinsky M: A comparison of phenytoin-loading techniques in the emergency department. Acad Emerg Med. 2004 Mar;11(3):244-52. [Article]
- Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Activator
- General Function
- Zinc ion binding
- Specific Function
- Nuclear receptor that binds and is activated by variety of endogenous and xenobiotic compounds. Transcription factor that activates the transcription of multiple genes involved in the metabolism an...
- Gene Name
- NR1I2
- Uniprot ID
- O75469
- Uniprot Name
- Nuclear receptor subfamily 1 group I member 2
- Molecular Weight
- 49761.245 Da
References
- Kobayashi K, Yamagami S, Higuchi T, Hosokawa M, Chiba K: Key structural features of ligands for activation of human pregnane X receptor. Drug Metab Dispos. 2004 Apr;32(4):468-72. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- SubstrateInhibitor
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and im...
- Gene Name
- CYP2C19
- Uniprot ID
- P33261
- Uniprot Name
- Cytochrome P450 2C19
- Molecular Weight
- 55930.545 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Zhang T, Zhu Y, Gunaratna C: Rapid and quantitative determination of metabolites from multiple cytochrome P450 probe substrates by gradient liquid chromatography-electrospray ionization-ion trap mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Nov 25;780(2):371-9. [Article]
- Ghahramani P, Ellis SW, Lennard MS, Ramsay LE, Tucker GT: Cytochromes P450 mediating the N-demethylation of amitriptyline. Br J Clin Pharmacol. 1997 Feb;43(2):137-44. [Article]
- Flockhart Table of Drug Interactions [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2B6
- Uniprot ID
- P20813
- Uniprot Name
- Cytochrome P450 2B6
- Molecular Weight
- 56277.81 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
- Lewis DF, Modi S, Dickins M: Structure-activity relationship for human cytochrome P450 substrates and inhibitors. Drug Metab Rev. 2002 Feb-May;34(1-2):69-82. [Article]
- Heyn H, White RB, Stevens JC: Catalytic role of cytochrome P4502B6 in the N-demethylation of S-mephenytoin. Drug Metab Dispos. 1996 Sep;24(9):948-54. [Article]
- Rendic S: Summary of information on human CYP enzymes: human P450 metabolism data. Drug Metab Rev. 2002 Feb-May;34(1-2):83-448. [Article]
- Source [Link]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Coller JK, Somogyi AA, Bochner F: Comparison of (S)-mephenytoin and proguanil oxidation in vitro: contribution of several CYP isoforms. Br J Clin Pharmacol. 1999 Aug;48(2):158-67. [Article]
- Koyama E, Chiba K, Tani M, Ishizaki T: Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. J Pharmacol Exp Ther. 1997 Jun;281(3):1199-210. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
- Gene Name
- CYP2D6
- Uniprot ID
- P10635
- Uniprot Name
- Cytochrome P450 2D6
- Molecular Weight
- 55768.94 Da
References
- Koyama E, Chiba K, Tani M, Ishizaki T: Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. J Pharmacol Exp Ther. 1997 Jun;281(3):1199-210. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C9
- Uniprot ID
- P11712
- Uniprot Name
- Cytochrome P450 2C9
- Molecular Weight
- 55627.365 Da
References
- Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
Carriers
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- No
- Actions
- Substrate
- General Function
- Serine-type endopeptidase inhibitor activity
- Specific Function
- Major thyroid hormone transport protein in serum.
- Gene Name
- SERPINA7
- Uniprot ID
- P05543
- Uniprot Name
- Thyroxine-binding globulin
- Molecular Weight
- 46324.12 Da
References
- CYTOMEL (liothyronine) FDA label [File]
Drug created at June 13, 2005 13:24 / Updated at November 03, 2023 23:43