Imotine

Abstract: Imotine ((S)-3-(N-Methylpyrollidino)-6-methyl-pyridine Benzoate; CAS 2861225-70-7) is a new non-nicotine compound that is reported to have Central Nervous System activity similar to nicotine. Imotine exists as the s-isomer. The compound is not manufactured from nicotine and does not contain any nicotine nor tobacco specific nitrosamine impurities. Analysis of the pure material did not reveal any chemicals of toxicologic concern. The pKa1 and pKa2 are reported to be 8.26 and 3.75 (respectively) as compared to 8.04 and 2.91 for nicotine. The compound is reported to be about 2.6 times more potent than s-nicotine on a molar basis in a mouse LD50 study. The compound is reported to have a similar affinity (Ki= 1.8 nM) for rat brain nicotinic acetylcholinergic receptors (nAChRs) as nicotine (Ki= 1.26 nM). Specific receptor binding data using [3H](-)-nicotine in rat brain (minus cerebellum) preparations containing nAchR alpha4-beta2 subunits showed a Ki of 1.8 nM compared to a Ki= of 2nM for nicotine. It has been concluded that the activity of Imotine is related to its structure and lipophilicity.