Metabolic Fate of 1,1-Dimethyl-5-methoxy-3-(dithien-2-ylmethylene)piperidinium Bromide (SA-504). I. Biliary Metabolites in Rats

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Isolation and characterization of biliary metabolites of SA-504,a new anticholinergic drug, were studied in rats. More than 70% of the radioactivity excreted in 3 hr bile of rats given ^<14>C-SA-504 was found to be due to metabolites. Fifteen metabolites were separated from bile of rats dosed with ^<14>C-SA-504,and eleven metabolites were characterized. Most of characterized metabolites were conjugated with GSH, cysteinylglycine, cysteine or N-acetylcysteine. The presence of the glycol derivative of SA-504 and tertiary amine N-oxide of SA-504 as minor metabolites was demonstrated. The oxidation of SA-504 by rat liver microsomes suggested that the epoxide was formed as an intermediate. From these facts, it seems likely to conclude that metabolic pathways of SA-504 consists of epoxidation, GSH conjugation and hydration of the epoxide, cleavage of C-C bond, N-demethylation and N-oxidation and the the main metabolic pathway of SA-504 is epoxidation followed by GSH conjugation.
公益社団法人日本薬学会の論文
1973-08-25