Microbial Models of Mammalian MetabolismO-Demethylations of Papaverine

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Abstract
1. Papaverine is converted to its 4'-, 6- and 7-desmethyl metabolites when incubated with hepatic microsomal preparations from phenobarbital-induced rats. The 7-desmethyl compound was predominantly formed in these studies. When incubated with guinea-pig microsomal preparations, papaverine was converted to its 6- and 4'-desmethyl metabolites in approximately equal amounts. 2. The O-demethylation of papaverine was studied with sixty microorganisms. Ten organisms (including Aspergillus, Cunninghamella and Strep-tomyces species) were found to actively metabolize this drug in a manner similar to that of mammals. 3. A strain of Aspergillus alliaceus was used to produce gram quantities of the mammalian metabolite, 6-desmethylpapaverine. Preparative amounts of 4'-desmethylpapaverine, a major mammalian metabolite of papaverine in vivo was produced with a strain of Cunninghamella echimulata