Drug Information

Drug (ID: DG00596) and It's Reported Resistant Information

• Name: Phenytoin
• Synonyms: Phenytoin; 5,5-DIPHENYLHYDANTOIN; 57-41-0; Diphenylhydantoin; Dilantin; 5,5-diphenylimidazolidine-2,4-dione; Phenytoine; Zentropil; Epamin; Dihydantoin; Aleviatin; Dilabid; Diphantoin; Diphenylan; Lepitoin; Diphedan; Fenylepsin; Phentytoin; Sodanton; Difenin; Dihycon; Lehydan; Diphenylhydatanoin; Dantoinal; Di-Hydan; Dilantine; Dillantin; Diphenine; Diphentyn; Ditoinate; Elepsindon; Epilantin; Fenitoina; Fenytoine; Hidantilo; Hidantina; Hidantomin; Hydantoinal; Kessodanten; Phanantin; Phanatine; Phenatoine; Sodantoin; Sylantoic; Thilophenyl; Zentronal; Auranile; Dantinal; Dantoine; Difetoin; Difhydan; Dintoin; Dintoina; Diphedal; Diphenin; Enkelfel; Epifenyl; Epihydan; Fentoin; Hidantal; Hydantal; Idantoil; Idantoin; Labopal; Phentoin; Ritmenal; Saceril; Sanepil; Silantin; Solantin; Danten; Denyl; Epelin; Epinat; Epised; Eptal; Hidan; Lepsin; Ekko; Ictalis simple; Toin unicelles; Dilantin acid; Dantoinal klinos; Om-Hydantoine; Di-Phetine; Epdantoine simple; Hidantina vitoria; Gerot-epilan-D; Epilan-D; Neosidantoina; Comitoina; Hidantina senosian; Hydantol; Minetoin; Novantoina; Causoin; Convul; Di-Lan; Ekko capsules; Neos-Hidantoina; 2,4-Imidazolidinedione, 5,5-diphenyl-; Om hidantoina simple; TOIN; Phenhydanin; Phenytex; Phenytoinum; Sinergina; Sodanthon; Iphenylhydantoin; Phenytoin-Gerot; Difenilhidantoina; Fenytoin Dak; Didan TDC 250; Dilantin-125; Epdantoin Simple; Phenytoin AWD; Epilan D; 5,5-Diphenyl-2,4-imidazolidinedione; Diphenat; Hindatal; Hydantin; Epanutin; Fenitoina [INN-Spanish]; Phenytoine [INN-French]; Phenytoinum [INN-Latin]; Difenilhidantoina [Spanish]; Diphenylhydantoine [French]; 5,5-Dwufenylohydantoina; Antisacer; Fenantoin Mn Pharma; Diphenylhydantoine; Di-Lan (VAN); PHENYTOIN SODIUM; Diphenylhydantoin (VAN); Diphentoin; DILANTIN-30; Solantoin; Solantyl; Eptoin; DPH (VAN); PHENYTEK; 5,5-Diphenylimidazolidin-2,4-dione; 5,5-Diphenyl-imidazolidine-2,4-dione; 5,5-Diphenylhydantoin (IUPAC); 5,5-Dwufenylohydantoina [Polish]; Hydantoin, 5,5-diphenyl-; CCRIS 515; CHEBI:8107; NCI-C55765; 5,5-Diphenylhydantoin (phenytoin); UNII-6158TKW0C5; Diphenylan sodium; AI3-52498; 5,5-diphenyl hydantoin; Dilantin (TN); Novophenytoin; MFCD00005264; MLS000069789; Citrulliamon; Phenitoin; 5,5-diphenyltetrahydro-1H-2,4-imidazoledione; Fenidantoin s; NSC8722; 6158TKW0C5; NSC-8722; Epasmir 5; NCGC00021139-03; SMR000059026; DSSTox_CID_541; Fenidantoin 's'; DSSTox_RID_75650; DSSTox_GSID_20541; Epasmir '5'; Didan-tdc-250; CAS-57-41-0; phenytoin (PHN); component of Mebroin; fenidantoin ''s''; epasmir ''5''; NSC 8722; EINECS 200-328-6; SR-01000075211; IFLab1_000214; Fenidantoin 's'; HSDB 3160; Episar (Salt/Mix); Epasmir '5'; Aladdin (Salt/Mix); Alepsin (Salt/Mix); Epsolin (Salt/Mix); Phenytoin (Lepitoin); Tacosal (Salt/Mix); Phenytoin [USAN:USP:INN:BAN:JAN]; Antisacer (Salt/Mix); Epdantoin (Salt/Mix); Epileptin (Salt/Mix); Hydantoin,5-diphenyl-; Spectrum_001105; Fenigramon (Salt/Mix); Citrullamon (Salt/Mix); Opera_ID_394; 2, 5,5-diphenyl-; CHEMBL16; Spectrum2_001281; Spectrum3_000890; Spectrum4_000984; Spectrum5_001369; Lopac-D-4007; Epitope ID:117723; D 4007; SCHEMBL3440; BIDD:PXR0090; Lopac0_000329; Lopac0_000378; Oprea1_373280; BSPBio_001437; KBioGR_001387; KBioSS_001585; MLS001074087; MLS002454401; BIDD:GT0625; DivK1c_000507; Soluble phenytoin (Salt/Mix); SPBio_001281; Phenytoin (JP17/USP/INN); GTPL2624; 2-hydroxy-5,5-diphenyl-3,5-dihydro-4H-imidazol-4-one; DTXSID8020541; KBio1_000507; KBio2_001585; KBio2_004153; KBio2_006721; KBio3_001780; WLN: T5MVMV EHJ ER& ER; 5,5-Diphenylhydantoin, >=99%; NINDS_000507; Phenytoin 1.0 mg/ml in Methanol; SM-88 COMPONENT PHENYTOIN; HMS1412J16; HMS1694O05; HMS1791H19; HMS1989H19; HMS2089E11; HMS2236J06; HMS3261K17; HMS3402H19; HMS3657O03; BCP05960; HY-B0448; Hydantoin, 5,5-diphenyl- (8CI); ZINC2510358; Tox21_110861; Tox21_202299; Tox21_300281; Tox21_500378; AC-376; BDBM50003655; BDBM50101816; s2525; STK058029; STK182871; STL454130; AKOS000416887; AKOS003245432; Tox21_110861_1; 5,5-diphenylimidazolidine-2,4-dione.; CCG-104011; CCG-221682; DB00252; LP00378; MCULE-2376673346; Phenytoin 1000 microg/mL in Methanol; 5,5-di(phenyl)imidazolidine-2,4-dione; IDI1_000507; IDI1_008433; NCGC00015342-01; NCGC00015342-02; NCGC00015342-03; NCGC00015342-04; NCGC00015342-05; NCGC00015342-06; NCGC00015342-07; NCGC00015342-08; NCGC00015342-09; NCGC00015342-10; NCGC00015342-11; NCGC00015342-12; NCGC00021139-01; NCGC00021139-02; NCGC00021139-04; NCGC00021139-05; NCGC00021139-06; NCGC00021139-07; NCGC00021139-08; NCGC00021139-09; NCGC00021139-10; NCGC00021139-11; NCGC00091492-01; NCGC00091492-02; NCGC00091492-03; NCGC00091492-04; NCGC00091492-05; NCGC00093810-01; NCGC00093810-02; NCGC00254135-01; NCGC00259848-01; NCGC00261063-01; 5,5- Diphenyl- 2,4- imidazolidinedione; 5,5-Diphenyl-1H-imidazolidine-2,4-dione; D0894; EU-0100378; FT-0667653; FT-0699999; P-235; SW203757-2; EN300-16818; 5,5-diphenylimidazolidine-2,4-dione;Phenytoin; C07443; D00512; E76094; 2,4-Imidazolidinedione, 5,5-diphenyl- (9CI); 5,5-diphenyl-1H-imidazole-2,4(3H,5H)-dione; AB00374253-10; AB00374253-11; AB00374253_13; A831435; Q410400; SR-01000003141; SR-01000003141-8; SR-01000075211-2; W-105468; BRD-K55930204-001-02-7; BRD-K55930204-236-11-0; Z56786458; 4-hydroxy-5,5-diphenyl-1,5-dihydro-2H-imidazol-2-one; F0020-1370; Phenytoin, European Pharmacopoeia (EP) Reference Standard; Phenytoin, United States Pharmacopeia (USP) Reference Standard; 5,5-Diphenylhydantoin solution, drug standard, 1.0 mg/mL in methanol; Phenytoin, Pharmaceutical Secondary Standard; Certified Reference Material; Phenytoin for system suitability, European Pharmacopoeia (EP) Reference Standard; Phenytoin solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material
• Indication:
  In total 1 Indication(s)
  Epilepsy [ICD-11: 8A60]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
  Status epilepticus [ICD-11: 8A66]; [2]
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Epilepsy [ICD-11: 8A60]; [1]
• Target: Sodium channel unspecific (NaC); NOUNIPROTAC; [1]
• Formula: C15H12N2O2
• IsoSMILES: C1=CC=C(C=C1)C2(C(=O)NC(=O)N2)C3=CC=CC=C3
• InChI: 1S/C15H12N2O2/c18-13-15(17-14(19)16-13,11-7-3-1-4-8-11)12-9-5-2-6-10-12/h1-10H,(H2,16,17,18,19)
• InChIKey: CXOFVDLJLONNDW-UHFFFAOYSA-N
• PubChem CID: 1775
• ChEBI ID: CHEBI:8107
• TTD Drug ID: D0E4DW
• VARIDT ID: DR00431
• INTEDE ID: DR1282
• DrugBank ID: DB00252

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-08: Nervous system diseases

Epilepsy [ICD-11: 8A60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Glutathione synthetase (GSH) [3]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: Ellman assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Key Molecule: Quinone reductase 1 (NQO1) [3]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Nrf2 signaling pathway; Inhibition; hsa05208
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: ELISA assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [1]

• Resistant Disease: Epilepsy [ICD-11: 8A60.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Mechanism Description: Comparing phenytoin brain/plasma ratio in mdr1 knockout mice with this ratio in mice with kainate-induced overexpression of Pgp indicated that Pgp can affect up to about 70% of phenytoin brain uptake. In epileptic rats, van Vliet et al reported decreased brain levels of phenytoin that were restricted to brain regions with increased expression of Pgp, which could be counteracted by inhibiting Pgp.

Status epilepticus [ICD-11: 8A66]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]

• Resistant Disease: Status epilepticus [ICD-11: 8A66.0]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Identified from the Human Clinical Data
• Mechanism Description: Pgp is involved in the resistance to phenytoin and phenobarbital but not diazepam.

References

• Ref 1: Drug Resistance in Epilepsy: Clinical Impact, Potential Mechanisms, and New Innovative Treatment Options .Pharmacol Rev. 2020 Jul;72(3):606-638. doi: 10.1124/pr.120.019539. 10.1124/pr.120.019539
• Ref 2: Mechanisms of drug resistance in status epilepticus .Epilepsia. 2007;48 Suppl 8:74-7. doi: 10.1111/j.1528-1167.2007.01357.x. 10.1111/j.1528-1167.2007.01357.x
• Ref 3: Attenuation of mitochondrial refractory epilepsy in rotenone corneal kindling model of drug resistance by idebenone: An approach to bypass mitochondrial complex I. Epilepsy Res. 2024 Nov;207:107458.