FORMATION OF NORNICOTINE AND OTHER METABOLITES FROM NICOTINE IN VITRO AND IN VIVO

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Abstract
Nornicotine and formaldehyde were formed from nicotine by an enzymatic preparation from rabbit liver. Nornicotine was identified by paper chromatography and was isolated and characterized by physical and chemical methods. Incubation of nornicotine with the same test system gave rise to demethylcotinine. Demethylcotinine was also found in chromatograms of liver extracts following the intravenous administration of nornicotine to the rabbit. Chromatograms from liver, kidney, and urine extracts showed the formation of nornicotine, cotinine, demethylcotinine, and nicotine-1′-oxide, following the intravenous administration of nicotine to the intact rabbit. These metabolic studies indicated that nicotine is demethylated to nornicotine which is further oxidized to demethylcotinine.