Molecular Pharmacology, Vol 2, 117-124, Copyright © 1966 by the American Society for Pharmacology and Experimental Therapeutics

The Metabolism of C¹⁴ 2-PAM in the Isolated Perfused Rat Liver

IV. 1-Methyl-2-Pyridone

¹ Department of Pharmacology, Marquette University School of Medicine, Milwaukee, Wisconsin, 2 and The University of Wisconsin School of Pharmacy and the Department of Pharmacology and Toxicology, School of Medicine, Madison, Wisconsin

The metabolic disposition of radioactive 1-methyl-2-aldoximinopyridinium iodide-1-¹⁴C (2-PAM) was investigated in the isolated perfused rat liver. In addition to the two metabolites already reported by our laboratory, a third metabolite of 2-PAM, 1-methyl-2-pyridone, has been isolated from the liver perfusate. The isolation procedures employed were ethanol and chloroform extraction, charcoal adsorption chromatography, paper electrophoresis, paper chromatography, and ion exchange chromatography. Characterization of the metabolite was accomplished by comparing its chemical, spectral, chromatographic, and electrophoretic properties with those of authentic 1-methyl-2-pyridone. The chemical, spectral, chromatographic and electrophoretic properties of this metabolite indicate that the compound is 1-methyl-2-pyridone. Metabolic pathways for the formation of 1-methyl-2-pyridone from 2-PAM and the possible molecular mechanisms involved in the various biotransformation reactions were proposed. The role of 1-methyl-2-pyridone and its intermediate in the conversion of 2-PAM to a 2-0-conjugate pyridinium ion was discussed.

Note:
ACKNOWLEDGMENT The authors are grateful to Professor N. E. Hoffman for the use of the gas chromatograph and to Professor E. M. Kosower and Dr. J. W. Patton for many valuable discussions and helpful suggestions. This work was supported in part by funds from the Office of Naval Research (Nonr-1202) and the National Institutes of Health, United States Public Health Service (MH10109 and NB 04541).