Formation of Nornicotine and Other Metabolites From Nicotine in Vitro and in Vivo

Abstract

Sornicotine and for~naldehyde were formed from nicotine by an enzymatic preparation from rabbit liver. Nornicotine was identified by paper chromatography and \\.as isolated and characterized by physical and chemical methods. Incubation of nornicotine with the same test system gave rise to demethl-lcotinine. Demethylcoti~~ine was also found in chromatograms of liver extracts following the intral-enous administration of nornicotine to the rabbit. Chromatograms from liver, kidne~-, ant1 urine extracts showed the formation of nornicotine, cotinine, d e n~e t h j Icotinine, and nicotine-1'-oxide, following the intravenous administration of nicotine to the intact rabbit. 'l'hese metabolic studies indicated that nicotine is tlemethj-lated to nornicotine which is further oxidized to demeth~.lcoti~~inc.

The metabolism of [14C]nicotine in the cat

“…Rp erebrospinal fluid values of these compounds, shownl in Table 1, were avenous injection consistent with those reported in the literature a/kg.). Artificial (Papadopoulos, 1964a). In addition, at least five as Ligh the cerebral yet unidentified radioactive materials were found cal bars represent in liver, two being present also in urine extracts.…”

Metabolism and Disposition Kinetics of Nicotine

“…8) were recovered from urine extracts, but no quantitative data were obtained. Metabolism of nornicotine by rabbits was reported by Papadopoulos (1964). Unchanged nornicotine, norcotinine, and an unidentified metabolite were detected by thin layer chromatographic analysis following an intravenous injection or after incubation with liver homogenates.…”

“…Animal studies have demonstrated the existence of both of these pathways. Wada et al (1961) and Papadopoulos (1964) reported that norcotinine is a metabolite of nornicotine, and Harke et al (1974) detected norcotinine in urine of pigs following cotinine administration. From studies in which deuterium-labeled nicotine and cotinine were administered, we have obtained evidence that both pathways occur in humans as well (P. Jacob III, L. Yu, and N. L. Benowitz, unpublished data).…”

Transformations involving the pyrrolidine ring of nicotine

“…(JEt Me (7) The n.m.r. spectra of the 4'-alkylnicotines, and in particular that of the 4',4'-dimethyl derivative which is relatively simple, confirm the proton assignments originally reported 28 for nicotine itself.…”