title: Impairment of debrisoquine 4-hydroxylase and related monooxygenase activities in the rat following treatment with propranolol.
abstract: The effect of repetitive oral administration of propranolol on hepatic microsomal drug metabolizing enzyme activities in the rat was investigated. Propranolol ring (4-, 5- and 7-)hydroxylase activities were markedly decreased, but, interestingly, N-desisopropylase activity was increased after propranolol administration. A marked decrease in enzyme activity after propranolol pretreatment was also observed with debrisoquine 4-hydroxylation. In addition, a similar decrease was observed with imipramine 2-hydroxylation which co-segregates with debrisoquine/sparteine type polymorphic drug oxidation, but not with imipramine N-demethylation. These results suggest the selective impairment of debrisoquine 4-hydroxylase by propranolol pretreatment.
authors.affiliation: Department of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Masubuchi
authors.forename: S
authors.initials: S
authors.lastname: Fujita
authors.forename: M
authors.initials: M
authors.lastname: Chiba
authors.forename: N
authors.initials: N
authors.lastname: Kagimoto
authors.forename: S
authors.initials: S
authors.lastname: Umeda
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D019389:Cytochrome P-450 CYP2D6; D065607:Cytochrome P-450 Enzyme Inhibitors; D003647:Debrisoquin / Q000378:metabolism; D007099:Imipramine / Q000378:metabolism; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors*; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D011433:Propranolol / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D011433:Propranolol; D006899:Mixed Function Oxygenases; D010105:Oxygenases; D019389:Cytochrome P-450 CYP2D6; D007099:Imipramine; D003647:Debrisoquin