6-Methylnicotine

6-Methylnicotine (6-MN) is a nicotine analogue in which a methyl group is added at the 6-position of the pyridine ring. It has been identified in certain electronic cigarettes and oral pouch products marketed as nicotine alternatives, sometimes under the trade names Metatine (in disposables) and Nixodine-S (sold as a benzoate salt or free base). Studies in cells, animal models, and early human biomonitoring indicate higher activity at nicotinic acetylcholine receptors and differences in toxicity and metabolism compared with nicotine. Although sometimes marketed as "not made or derived from tobacco", a 2025 analytical study reported trace natural occurrence of 6-MN in tobacco at a mean of 0.32 micrograms per gram (μg/g) and detected low-μg/mL levels in some previously analysed high-nicotine e-liquids, complicating origin-based regulatory claims. Reports of nicotine analogues date to the early 1960s. In 1963, Erdtman, Haglid and Wellings described synthetic analogues of nicotine, establishing early approaches to ring- and side-chain modification of the alkaloid. In 1967, Haglid demonstrated that treatment of nicotine with methyllithium furnished multiple methylnicotine isomers, including 6-methylnicotine; the study detailed conditions and product distributions. Industry-affiliated work expanded these routes in the early 1980s. A 1981 communication showed that methylmagnesium bromide addition to nicotine N-oxide provided both 2- and 6-methylnicotine, and that methyllithium could favor 2-substitution under certain conditions. A 1983 full paper from the Philip Morris U.S.A. Research Center (Richmond, Virginia) mapped reaction pathways and racemization behaviour for organometallic methylations of nicotine and nicotine N-oxide, reporting formation of 2-, 4- and 6-methylnicotines under varied conditions.