RT Journal Article SR Electronic T1 Metabolic N-demethylation of 1,3-bis[[1-cycloheptyl-3-(p- dimethylaminophenyl)ureido]methyl]benzene dihydrochloride, a novel acyl-coenzyme A:cholesterol acyltransferase inhibitor. JF Drug Metabolism and Disposition JO Drug Metab Dispos FD American Society for Pharmacology and Experimental Therapeutics SP 524 OP 529 VO 21 IS 3 A1 T Uchida A1 T Usui A1 T Teramura A1 T Watanabe A1 S Higuchi YR 1993 UL http://dmd.aspetjournals.org/content/21/3/524.abstract AB The metabolism of 1,3-bis[[1-cycloheptyl-3-(p-dimethylamino- phenyl)ureido]methyl]benzene dihydrochloride (YM17E) in rat liver microsomes was investigated. After incubation of YM17E with rat liver microsomes in the presence of NADPH, a significant amount of YM17E was consumed and several products appeared. The structures of these products were identified by thermospray-linked LC/MS. By comparison of fragmentation patterns between these products and authentic compounds, five metabolites were eventually identified. All five metabolites--termed M1, M2-a, M2-b, M3, and M4--were sequentially formed through N-demethylation. The formation of these metabolites was NADPH-dependent, and was inhibited by SKF-525A, metyrapone, and carbon monoxide, which are inhibitors of cytochrome P-450. These results suggest that N-demethylation of YM17E is one of the main pathways of its biotransformation, and that this metabolism is catalyzed by cytochrome P-450-mediated monooxygenase.