Metabolism of metyrapone. III. Formation of an alpha-pyridone metabolite by rat hepatic soluble enzymes.

Incubation of 2-methyl-1,2-bis(3-pyridyl)-1-propanone (metyrapone) with rat hepatic 140,000 g supernatant fraction and an NADPH-regenerating system leads to the formation of 2-methyl-1,2-bis(3-pyridyl)-1-propanol (metyrapol), and one other metabolite identified as 2-methyl-1-[3-(6-oxopyridyl)]-2-(3-pyridyl)-1-propanone by a combination of various spectrometric techniques (UV, IR, NMR, and mass spectrometry). Incubation of metyrapol under similar conditions did not lead to the formation of any detectable metabolites. Hitherto, no reports have described the in vitro biotransformation of an unquaternized pyridine molecule to an alpha-pyridone metabolite.