PT  - JOURNAL ARTICLE
AU  - J R Cashman
AU  - J Proudfoot
AU  - D W Pate
AU  - T Högberg
TI  - Stereoselective N-oxygenation of zimeldine and homozimeldine by the flavin-containing monooxygenase.
DP  - 1988 Jul 01
TA  - Drug Metabolism and Disposition
PG  - 616--622
VI  - 16
IP  - 4
4099  - http://dmd.aspetjournals.org/content/16/4/616.short
4100  - http://dmd.aspetjournals.org/content/16/4/616.full
SO  - Drug Metab Dispos1988 Jul 01; 16
AB  - The metabolism of (Z)- and (E)-zimeldine and (Z)- and (E)-homozimeldine in hepatic rat and hog microsomes is described. The major metabolite observed in all cases examined was the tertiary amine N-oxide and it was formed at a rate 7-20 times that of norzimeldine or homonorzimeldine. N-Oxygenation requires NADPH and is stimulated by n-octylamine. Thiobenzamide and methimazole significantly inhibit N-oxide formation whereas heat pretreatment of microsomes completely abolishes N-oxide formation, strongly suggesting that zimeldine N-oxygenation if solely dependent on the flavin-containing monooxygenase. Hog liver microsomes N-oxygenate the Z-allylic and homoallylic tertiary amines in marked preference to the E-isomers, whereas rat liver microsomes N-oxygenate E-isomers to a greater extent than Z-isomers. Thus, opposite stereoselectivity for zimeldine N-oxygenation occurs in rat liver and hog liver microsomes.