PT  - JOURNAL ARTICLE
AU  - PAULO M. S. MIRANDA
AU  - JAMES L. WAY
TI  - The Metabolism of C<sup>14</sup> 2-PAM in the Isolated Perfused Rat Liver
DP  - 1966 Apr 01
TA  - Molecular Pharmacology
PG  - 117--124
VI  - 2
IP  - 2
4099  - http://molpharm.aspetjournals.org/content/2/2/117.short
4100  - http://molpharm.aspetjournals.org/content/2/2/117.full
SO  - Mol Pharmacol1966 Apr 01; 2
AB  - 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. 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).