title: Imipramine for Cytochrome P450 Activity Determination: a Multiple-species Metabolic Probe.
abstract: Imipramine is metabolized in vitro by rat, mouse or human microsomes to several metabolites including 2-hydroxyimipramine, 2-hydroxydesipramine, desipramine, didesmethylimipramine and imipramine-N-oxide. Heat treatment (which inhibits FMO), verified the role of this group of enzymes in the oxidation of imipramine to imipramine N-oxide. These studies demonstrate that while rats and humans showed similar metabolic profiles, producing several minor metabolites in addition to the 2-hydroxyimipramne and desipramine, differences were seen in the mouse microsomes. In these samples, few minor metabolites were produced. In addition, imipramine N-oxide was the major metabolite in mouse, whereas none was detected in human samples. To conclude, the metabolic profile of imipramine can be used to reveal a number of cytochrome P450 enzymes active in microsomal fractions.
authors.affiliation: ECVAM, Institute of Health and Consumer Protection, Ispra, Italy; FRAME Alternatives Laboratory, School of Biomedical Sciences, Nottingham University, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bull
authors.forename: P
authors.initials: P
authors.lastname: Catalani
authors.forename: M
authors.initials: M
authors.lastname: Garle
authors.forename: S
authors.initials: S
authors.lastname: Coecke
authors.forename: R
authors.initials: R
authors.lastname: Clothier