TY - JOUR T1 - Stereoselective N-oxygenation of zimeldine and homozimeldine by the flavin-containing monooxygenase. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 616 LP - 622 VL - 16 IS - 4 AU - J R Cashman AU - J Proudfoot AU - D W Pate AU - T Högberg Y1 - 1988/07/01 UR - http://dmd.aspetjournals.org/content/16/4/616.abstract N2 - 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. ER -