RT Journal Article
SR Electronic
T1 Effects of genetic or chemically induced diabetes on imipramine metabolism. Respective involvement of flavin monooxygenase and cytochrome P-450-dependent monooxygenases.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 524
OP 528
VO 15
IS 4
A1 Rouer, E
A1 Lemoine, A
A1 Cresteil, T
A1 Rouet, P
A1 Leroux, J P
YR 1987
UL http://dmd.aspetjournals.org/content/15/4/524.abstract
AB Imipramine metabolism has been studied in both type I (streptozotocin-induced insulin-deficient) and type II (genetically insulin-resistant) diabetes in mice. In both types of diabetes, the formation of imipramine N-oxide is increased. In type I diabetes, desmethyl- and 2-hydroxyimipramine are additionally increased. The inhibition of imipramine metabolism by anti-cytochrome P-450 reductase antibodies led to the conclusion that cytochrome P-450-dependent monooxygenases are not involved in the N-oxidation of imipramine. This metabolic route is only supported by the flavin monooxygenase, whose activity is increased by diabetes. The pharmacological implications of altered imipramine metabolism in diabetic states are discussed in relation to the drug metabolism in human diabetes.