URINARY METABOLITE OF 1,1'-TRIMETHYLENEBIS (4-ALDOXIMINOPYRIDINIUM) DIBROMIDE (TMB-4) IN THE RAT. I. TRIMETHYLENE-1-(4-ALDOXIMINOPYRIDINIUM)-1'-(4-CYANOPYRIDINIUM) DIBROMIDE

¹ Department of Pharmacology, Washington State University, Colleges of Pharmacy and Veterinary Medicine, Pullman, Washington, and Marquette University School of Medicine, Milwaukee, Wisconsin

Isotopically labeled 1,1'-trimethylene-bis(4-aldoximinopyridinium)dibromide-1,1'-¹⁴C (TMB-4) was prepared and its physiological disposition was investigated in the intact rat. Rats received the antagonist i.p. and urine was collected over a period of 24 hours. Isolation of a metabolite of TMB-4, namely trimethylene-1-(4-aldoximinopyridinium)-1'-(4-cyanopyridinium) ion, from the urine was accomplished by ethanol extraction, charcoal adsorption chromatography, ion exchange chromatography, paper chromatography and paper electrophoresis. Characterization of this metabolite was carried out by comparing its chemical, spectral, chromatographic and electrophoretic properties with those of authentic trimethylene-1-(4-aldoximinopyridinium)-1'-(4-cyanopyridinium) ion. The properties of this metabolite were found to be consistent with those of trimethylene-1-(4-aldoximinopyridinium)-1'-(4-cyanopyridinium)dibromide. The possible reaction mechanisms involved in the biochemical pathways for the conversion of TMB-4 to trimethylene-1-(4-aldoximinopyridinium)-1'-(4-cyanopyridinium) ion were discussed. The renal excretory pattern of TMB-4 indicated that this antagonist, like pralidoxime and most quaternary ammonium compounds, is rapidly excreted in the urine.