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Impairment of debrisoquine 4-hydroxylase and related monooxygenase activities in the rat following treatment with propranolol.

Authors
  • Masubuchi, Y
  • Fujita, S
  • Chiba, M
  • Kagimoto, N
  • Umeda, S
  • Suzuki, T
Type
Published Article
Journal
Biochemical Pharmacology
Publisher
Elsevier
Publication Date
Jan 01, 1991
Volume
41
Issue
6-7
Pages
861–865
Identifiers
PMID: 2009081
Source
Medline
License
Unknown

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.

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