title: Involvement of CYP3A4 in the metabolism of bromperidol in vitro.
abstract: In this study, human cytochrome P450 isoenzymes (CYP1A2, CYP2C19, CYP2D6, and CYP3A4) expressed in a cell line were used to elucidate their roles in the metabolism of bromperidol. We found that CYP3A4 catalyzes the N-dealkylation of bromperidol and its metabolite, reduced bromperidol. CYP3A4 also catalyzes the dehydration of bromperidol to bromperidol 1,2,3,6-tetrahydropyridine, metabolizes bromperidol to bromperidol pyridinium, and catalyzes the oxidation of reduced bromperidol back to bromperidol. CYP1A2, CYP2C19, and CYP2D6 do not catalyze these reactions.
authors.affiliation: Department of Psychiatry, Niigata University School of Medicine, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: T
authors.initials: T
authors.lastname: Someya
authors.forename: O
authors.initials: O
authors.lastname: Shioiri
authors.forename: T
authors.initials: T
authors.lastname: Koitabashi
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases; D002458:Cell Fractionation; D002460:Cell Line / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6 / Q000378:metabolism; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006220:Haloperidol / Q000031:analogs & derivatives* / Q000378:metabolism; D006801:Humans; D008861:Microsomes / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000378:metabolism*
chemical_list: D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; C104464:CYP3A protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D006220:Haloperidol; C006820:bromperidol