THE METABOLISM OF C¹⁴ 2-PAM IN THE ISOLATED PERFUSED RAT LIVER. III. 1-METHYL-2-CYANOPYRIDINIUM ION

¹ Department of Pharmacology, The University of Wisconsin Medical School, Madison, Wisconsin

Isotopically labeled 2-PAM (1-methyl-2-formylpyridinium iodide oxime-1-C¹⁴) was prepared and its metabolic disposition was investigated in the isolated perfused rat liver. Isolation of a second metabolite of 2-PAM, namely 1-methyl-2-cyanopyridinium ion, from the perfusate was accomplished by ethanol extraction, charcoal adsorption chromatography, ion exchange chromatography, paper chromatography and paper electrophoresis. The properties of this metabolite were found to be consistent with those of a 1-methyl-2-cyanopyridinium ion.

Characterization of this metabolite was carried out by comparing its chemical, spectral, chromatographic and electrophoretic properties with those of authentic 1-methyl-2-cyanopyridinium ion. The alkaline hydrolytic products of the metabolite and the 2-cyanopyridinium ion were compared with cyanide ion, 1-methyl-2-carbamidopyridinium ion and 1-methyl-2-pyridone.

The possible metabolic role of 2-cyanopyridinium ion as an intermediate for the conversion of 2-PAM to the 2-O-conjugate pyridinium ion and the possible reaction mechanisms involved in the conversion were considered.