title: Benzydamine N-oxygenation as a measure of flavin-containing monooxygenase activity.
abstract: Benzydamine is a nonsteroidal anti-inflammatory drug that undergoes flavin-containing monooxygenase (FMO)-dependent metabolism to a stable N-oxide. This metabolite can be quantified with high specificity and sensitivity by using a simple reverse-phase high-performance liquid chromatography (HPLC) assay with fluorescence detection. Studies with recombinant FMO enzymes demonstrate that FMOI and FMO3 are the primary catalysts of benzydamine N-oxygenation, with minimal contributions from cytochrome P450 enzymes. Investigations conducted with human liver microsomes confirm that FMO3, in large part, is responsible for benzydamine N-oxide formation in this tissue. These features render benzydamine a useful in vitro probe for FMO activity in a wide range of tissues and cell types. In addition, benzydamine appears to be a suitable in vivo probe for human liver FMO3. This chapter provides a detailed account of the experimental protocol for determining rates of formation of benzydamine N-oxide by FMO-containing enzyme fractions.
authors.affiliation: Department of Medicinal Chemistry, University of Washington, Seattle, USA.
authors.forename: Catherine K
authors.initials: CK
authors.lastname: Yeung
authors.forename: Allan E
authors.initials: AE
authors.lastname: Rettie
mesh_terms: D001591:Benzydamine / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D010100:Oxygen / Q000378:metabolism*; D010105:Oxygenases / Q000378:metabolism*
chemical_list: D001591:Benzydamine; D010105:Oxygenases; C020066:dimethylaniline monooxygenase (N-oxide forming); D010100:Oxygen