R. H. Meacham, E. Bowman, H. McKennis
Feb 10, 1972
Citations
0
Influential Citations
6
Citations
Quality indicators
Journal
The Journal of biological chemistry
Abstract
Abstract The metabolism of dihydrometanicotine was investigated in the rat and dog. In preliminary studies, dihydrometanicotine difumarate was administered to rats. The Rf values and retention times of methyl esters prepared from acidic Koenig-positive metabolites in the urine suggested the presence of 3-pyridylacetate and 4-(3-pyridyl)butyrate. Following administration of dihydrometanicotine difumarate to dogs, the pattern of excretion of acidic metabolites in the urine was similar to that found in the rat. Chemical conversion of the acidic metabolites to their methyl esters for separation by preparative gas chromatography afforded methyl 3-pyridylacetate and methyl 4-(3-pyridyl)butyrate. Methyl 3-pyridylacetate was identified by melting point, elemental analysis, and the infrared spectrum of its picric acid salt. Methyl 4-(3-pyridyl)butyrate was identified by mass spectroscopy and by the melting point, elemental analysis, and the infrared spectrum of the methyl ester picrate. Previous studies have provided evidence for the formation of 3-pyridylacetate from (-)nicotine via either (-)cotinine or (-)demethylcotinine. In view of the report (de Clercq, M., and Truhaut, R. (1962) Bull. Soc. Chim. Biol., 44, 227) that dihydrometanicotine is a metabolite of nicotine in the rat, the present findings in the rat and dog suggest a third alternate route (via dihydrometanicotine) to 3-pyridylacetate.