Phenytoin
Phenytoin (diphenylhydantoin), was formerly the most commonly used non-sedative antiepileptic and anticonvulsant agent used to treat and prevent generalized grand mal seizures and status epilepticus. Phenytoin is a hydantoin derivative. Phenytoin potentially acts by promoting sodium efflux from neurons located in the motor cortex reducing post-tetanic potentiation at synapses, preventing cortical seizure foci spreading to adjacent areas, stabilizing the threshold against hyperexcitability. In addition, this agent appears to reduce sensitivity of muscle spindles to stretch causing muscle relaxation. Phenytoin is an uncommon but well known cause of acute idiosyncratic drug induced liver disease that can be severe and even fatal. Phenytoin (diphenylhydantoin, dilantin) is metabolized by cytochrome P-450 monooxygenases to several oxidized products, including parahydroxylated and dihydrodiol metabolites . Arene oxides, which are reactive electrophilic compounds, are intermediates in these oxidative reactions. If not detoxified, arene oxide metabolites can covalently bind to cell macromolecules, resulting in cell death, mutation, tumors, birth defects, and, by acting as haptens, can lead to secondary immune phenomena.
General
Type : Not AlphaBeta Hydrolase target
Chemical_Nomenclature : 5,5-diphenylimidazolidine-2,4-dione
Canonical SMILES : C1=CC=C(C=C1)C2(C(=O)NC(=O)N2)C3=CC=CC=C3
InChI : 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
Other name(s) : 5,5-Diphenylhydantoin || Diphenylhydantoin || Dilantin || Phenytoine || Zentropil
MW : 252.27
Formula : C15H12N2O2
CAS_number : 57-41-0
PubChem : 1775
UniChem : CXOFVDLJLONNDW-UHFFFAOYSA-N
Target
Structures : No structure
Families : No family
References (30)
| Title : Evaluation of clinical and genetic factors in the population pharmacokinetics of carbamazepine - Yip_2021_Br.J.Clin.Pharmacol_87_2572 |
| Author(s) : Yip VLM , Pertinez H , Meng X , Maggs JL , Carr DF , Park BK , Marson AG , Pirmohamed M |
| Ref : British Journal of Clinical Pharmacology , 87 :2572 , 2021 |
| Abstract : |
| PubMedSearch : Yip_2021_Br.J.Clin.Pharmacol_87_2572 |
| PubMedID: 33217013 |
| Title : Evaluation of clinical and genetic factors in the population pharmacokinetics of carbamazepine - Yip_2021_Br.J.Clin.Pharmacol_87_2572 |
| Author(s) : Yip VLM , Pertinez H , Meng X , Maggs JL , Carr DF , Park BK , Marson AG , Pirmohamed M |
| Ref : British Journal of Clinical Pharmacology , 87 :2572 , 2021 |
| Abstract : |
| PubMedSearch : Yip_2021_Br.J.Clin.Pharmacol_87_2572 |
| PubMedID: 33217013 |
| Title : Evaluation of clinical and genetic factors in the population pharmacokinetics of carbamazepine - Yip_2021_Br.J.Clin.Pharmacol_87_2572 |
| Author(s) : Yip VLM , Pertinez H , Meng X , Maggs JL , Carr DF , Park BK , Marson AG , Pirmohamed M |
| Ref : British Journal of Clinical Pharmacology , 87 :2572 , 2021 |
| Abstract : |
| PubMedSearch : Yip_2021_Br.J.Clin.Pharmacol_87_2572 |
| PubMedID: 33217013 |
| Title : Role of CYP2C9, CYP2C19 and EPHX Polymorphism in the Pharmacokinetic of Phenytoin: A Study on Uruguayan Caucasian Subjects - Guevara_2017_Pharmaceuticals.(Basel)_10_ |
| Author(s) : Guevara N , Maldonado C , Uria M , Gonzalez R , Ibarra M , Alvariza S , Carozzi A , Azambuja C , Fagiolino P , Vazquez M |
| Ref : Pharmaceuticals (Basel) , 10 : , 2017 |
| Abstract : |
| PubMedSearch : Guevara_2017_Pharmaceuticals.(Basel)_10_ |
| PubMedID: 28820457 |
| Title : Role of CYP2C9, CYP2C19 and EPHX Polymorphism in the Pharmacokinetic of Phenytoin: A Study on Uruguayan Caucasian Subjects - Guevara_2017_Pharmaceuticals.(Basel)_10_ |
| Author(s) : Guevara N , Maldonado C , Uria M , Gonzalez R , Ibarra M , Alvariza S , Carozzi A , Azambuja C , Fagiolino P , Vazquez M |
| Ref : Pharmaceuticals (Basel) , 10 : , 2017 |
| Abstract : |
| PubMedSearch : Guevara_2017_Pharmaceuticals.(Basel)_10_ |
| PubMedID: 28820457 |
| Title : Role of CYP2C9, CYP2C19 and EPHX Polymorphism in the Pharmacokinetic of Phenytoin: A Study on Uruguayan Caucasian Subjects - Guevara_2017_Pharmaceuticals.(Basel)_10_ |
| Author(s) : Guevara N , Maldonado C , Uria M , Gonzalez R , Ibarra M , Alvariza S , Carozzi A , Azambuja C , Fagiolino P , Vazquez M |
| Ref : Pharmaceuticals (Basel) , 10 : , 2017 |
| Abstract : |
| PubMedSearch : Guevara_2017_Pharmaceuticals.(Basel)_10_ |
| PubMedID: 28820457 |
| Title : Phenytoin embryopathy: effect of epoxide hydrolase inhibitor on phenytoin exposure in utero in C57BL\/6J mice - Hartsfield_1995_Biochem.Mol.Med_56_131 |
| Author(s) : Hartsfield JK, Jr. , Holmes LB , Morel JG |
| Ref : Biochemical & Molecular Medicine , 56 :131 , 1995 |
| Abstract : |
| PubMedSearch : Hartsfield_1995_Biochem.Mol.Med_56_131 |
| PubMedID: 8825076 |
| Title : Phenytoin embryopathy: effect of epoxide hydrolase inhibitor on phenytoin exposure in utero in C57BL\/6J mice - Hartsfield_1995_Biochem.Mol.Med_56_131 |
| Author(s) : Hartsfield JK, Jr. , Holmes LB , Morel JG |
| Ref : Biochemical & Molecular Medicine , 56 :131 , 1995 |
| Abstract : |
| PubMedSearch : Hartsfield_1995_Biochem.Mol.Med_56_131 |
| PubMedID: 8825076 |
| Title : Phenytoin embryopathy: effect of epoxide hydrolase inhibitor on phenytoin exposure in utero in C57BL\/6J mice - Hartsfield_1995_Biochem.Mol.Med_56_131 |
| Author(s) : Hartsfield JK, Jr. , Holmes LB , Morel JG |
| Ref : Biochemical & Molecular Medicine , 56 :131 , 1995 |
| Abstract : |
| PubMedSearch : Hartsfield_1995_Biochem.Mol.Med_56_131 |
| PubMedID: 8825076 |
| Title : Differences in phenytoin biotransformation and susceptibility to congenital malformations: a review - Van Dyke_1991_DICP_25_987 |
| Author(s) : Van Dyke DC , Berg MJ , Olson CH |
| Ref : DICP , 25 :987 , 1991 |
| Abstract : |
| PubMedSearch : Van Dyke_1991_DICP_25_987 |
| PubMedID: 1683079 |
| Title : Differences in phenytoin biotransformation and susceptibility to congenital malformations: a review - Van Dyke_1991_DICP_25_987 |
| Author(s) : Van Dyke DC , Berg MJ , Olson CH |
| Ref : DICP , 25 :987 , 1991 |
| Abstract : |
| PubMedSearch : Van Dyke_1991_DICP_25_987 |
| PubMedID: 1683079 |
| Title : Differences in phenytoin biotransformation and susceptibility to congenital malformations: a review - Van Dyke_1991_DICP_25_987 |
| Author(s) : Van Dyke DC , Berg MJ , Olson CH |
| Ref : DICP , 25 :987 , 1991 |
| Abstract : |
| PubMedSearch : Van Dyke_1991_DICP_25_987 |
| PubMedID: 1683079 |
| Title : Inheritance of poor phenytoin parahydroxylation capacity in a Dutch family - Vermeij_1988_Clin.Pharmacol.Ther_44_588 |
| Author(s) : Vermeij P , Ferrari MD , Buruma OJ , Veenema H , de Wolff FA |
| Ref : Clinical Pharmacology & Therapeutics , 44 :588 , 1988 |
| Abstract : |
| PubMedSearch : Vermeij_1988_Clin.Pharmacol.Ther_44_588 |
| PubMedID: 3180640 |
| Title : Inheritance of poor phenytoin parahydroxylation capacity in a Dutch family - Vermeij_1988_Clin.Pharmacol.Ther_44_588 |
| Author(s) : Vermeij P , Ferrari MD , Buruma OJ , Veenema H , de Wolff FA |
| Ref : Clinical Pharmacology & Therapeutics , 44 :588 , 1988 |
| Abstract : |
| PubMedSearch : Vermeij_1988_Clin.Pharmacol.Ther_44_588 |
| PubMedID: 3180640 |
| Title : Inheritance of poor phenytoin parahydroxylation capacity in a Dutch family - Vermeij_1988_Clin.Pharmacol.Ther_44_588 |
| Author(s) : Vermeij P , Ferrari MD , Buruma OJ , Veenema H , de Wolff FA |
| Ref : Clinical Pharmacology & Therapeutics , 44 :588 , 1988 |
| Abstract : |
| PubMedSearch : Vermeij_1988_Clin.Pharmacol.Ther_44_588 |
| PubMedID: 3180640 |
| Title : Correlations between embryotoxic and genotoxic effects of phenytoin in mice - Barcellona_1987_Teratog.Carcinog.Mutagen_7_159 |
| Author(s) : Barcellona PS , Barale R , Campana A , Zucconi D , Rossi V , Caranti S |
| Ref : Teratog Carcinog Mutagen , 7 :159 , 1987 |
| Abstract : |
| PubMedSearch : Barcellona_1987_Teratog.Carcinog.Mutagen_7_159 |
| PubMedID: 2885938 |
| Title : Correlations between embryotoxic and genotoxic effects of phenytoin in mice - Barcellona_1987_Teratog.Carcinog.Mutagen_7_159 |
| Author(s) : Barcellona PS , Barale R , Campana A , Zucconi D , Rossi V , Caranti S |
| Ref : Teratog Carcinog Mutagen , 7 :159 , 1987 |
| Abstract : |
| PubMedSearch : Barcellona_1987_Teratog.Carcinog.Mutagen_7_159 |
| PubMedID: 2885938 |
| Title : Correlations between embryotoxic and genotoxic effects of phenytoin in mice - Barcellona_1987_Teratog.Carcinog.Mutagen_7_159 |
| Author(s) : Barcellona PS , Barale R , Campana A , Zucconi D , Rossi V , Caranti S |
| Ref : Teratog Carcinog Mutagen , 7 :159 , 1987 |
| Abstract : |
| PubMedSearch : Barcellona_1987_Teratog.Carcinog.Mutagen_7_159 |
| PubMedID: 2885938 |
| Title : Genetic predisposition to phenytoin-induced birth defects - Strickler_1985_Lancet_2_746 |
| Author(s) : Strickler SM , Dansky LV , Miller MA , Seni MH , Andermann E , Spielberg SP |
| Ref : Lancet , 2 :746 , 1985 |
| Abstract : |
| PubMedSearch : Strickler_1985_Lancet_2_746 |
| PubMedID: 2864485 |
| Title : Genetic predisposition to phenytoin-induced birth defects - Strickler_1985_Lancet_2_746 |
| Author(s) : Strickler SM , Dansky LV , Miller MA , Seni MH , Andermann E , Spielberg SP |
| Ref : Lancet , 2 :746 , 1985 |
| Abstract : |
| PubMedSearch : Strickler_1985_Lancet_2_746 |
| PubMedID: 2864485 |
| Title : Genetic predisposition to phenytoin-induced birth defects - Strickler_1985_Lancet_2_746 |
| Author(s) : Strickler SM , Dansky LV , Miller MA , Seni MH , Andermann E , Spielberg SP |
| Ref : Lancet , 2 :746 , 1985 |
| Abstract : |
| PubMedSearch : Strickler_1985_Lancet_2_746 |
| PubMedID: 2864485 |
| Title : Predisposition to phenytoin hepatotoxicity assessed in vitro - Spielberg_1981_N.Engl.J.Med_305_722 |
| Author(s) : Spielberg SP , Gordon GB , Blake DA , Goldstein DA , Herlong HF |
| Ref : N Engl J Med , 305 :722 , 1981 |
| Abstract : |
| PubMedSearch : Spielberg_1981_N.Engl.J.Med_305_722 |
| PubMedID: 6790991 |
| Title : Predisposition to phenytoin hepatotoxicity assessed in vitro - Spielberg_1981_N.Engl.J.Med_305_722 |
| Author(s) : Spielberg SP , Gordon GB , Blake DA , Goldstein DA , Herlong HF |
| Ref : N Engl J Med , 305 :722 , 1981 |
| Abstract : |
| PubMedSearch : Spielberg_1981_N.Engl.J.Med_305_722 |
| PubMedID: 6790991 |
| Title : Predisposition to phenytoin hepatotoxicity assessed in vitro - Spielberg_1981_N.Engl.J.Med_305_722 |
| Author(s) : Spielberg SP , Gordon GB , Blake DA , Goldstein DA , Herlong HF |
| Ref : N Engl J Med , 305 :722 , 1981 |
| Abstract : |
| PubMedSearch : Spielberg_1981_N.Engl.J.Med_305_722 |
| PubMedID: 6790991 |
| Title : Inheritance of phenytoin hypometabolism: a kinetic study of one family - |
| Author(s) : Vasko MR , Bell RD , Daly DD , Pippenger CE |
| Ref : Clinical Pharmacology & Therapeutics , 27 :96 , 1980 |
| PubMedID: 7351122 |
| Title : Inheritance of phenytoin hypometabolism: a kinetic study of one family - |
| Author(s) : Vasko MR , Bell RD , Daly DD , Pippenger CE |
| Ref : Clinical Pharmacology & Therapeutics , 27 :96 , 1980 |
| PubMedID: 7351122 |
| Title : Inheritance of phenytoin hypometabolism: a kinetic study of one family - |
| Author(s) : Vasko MR , Bell RD , Daly DD , Pippenger CE |
| Ref : Clinical Pharmacology & Therapeutics , 27 :96 , 1980 |
| PubMedID: 7351122 |
| Title : Phenytoin teratogenesis: correlation between embryopathic effect and covalent binding of putative arene oxide metabolite in gestational tissue - Martz_1977_J.Pharmacol.Exp.Ther_203_231 |
| Author(s) : Martz F , Failinger C, 3rd , Blake DA |
| Ref : Journal of Pharmacology & Experimental Therapeutics , 203 :231 , 1977 |
| Abstract : |
| PubMedSearch : Martz_1977_J.Pharmacol.Exp.Ther_203_231 |
| PubMedID: 909055 |
| Title : Phenytoin teratogenesis: correlation between embryopathic effect and covalent binding of putative arene oxide metabolite in gestational tissue - Martz_1977_J.Pharmacol.Exp.Ther_203_231 |
| Author(s) : Martz F , Failinger C, 3rd , Blake DA |
| Ref : Journal of Pharmacology & Experimental Therapeutics , 203 :231 , 1977 |
| Abstract : |
| PubMedSearch : Martz_1977_J.Pharmacol.Exp.Ther_203_231 |
| PubMedID: 909055 |
| Title : Phenytoin teratogenesis: correlation between embryopathic effect and covalent binding of putative arene oxide metabolite in gestational tissue - Martz_1977_J.Pharmacol.Exp.Ther_203_231 |
| Author(s) : Martz F , Failinger C, 3rd , Blake DA |
| Ref : Journal of Pharmacology & Experimental Therapeutics , 203 :231 , 1977 |
| Abstract : |
| PubMedSearch : Martz_1977_J.Pharmacol.Exp.Ther_203_231 |
| PubMedID: 909055 |