Nicotine is a natural alkaloid obtained from the dried leaves and stems of the nightshade family of pants, such as Nicotiana tabacum and Nicotiana rustica, where it occurs in concentrations of 0.5-8%. Cigarette tobacco varies in its nicotine content, but common blends contain 15-25 mg per cigarette, with a current trend towards lower levels. Nicotine is highly addictive substance, it exhibits a stimulant effect when adsorbed at 2 mg. Administration of higher doses could be harmful. Action of nicotine is mediated by nicotinic cholinergic receptors. Nicotine binds to the interface between two subunits of the receptors, opens the channel and allows the entry of sodium or calcium. The principal mediator of nicotine dependence is α4β2 nicotine receptor.

Nornicotine is a natural alkaloid produced by plants in the genus Nicotiana and is structurally related to nicotine. Nornicotine is the direct precursor of tobacco-specific nitrosamine N'-nitrosonornicotine, which is a highly potent human carcinogen. Nornicotine is an active nicotine metabolite, which accumulates in brain to pharmacologically relevant concentrations following repeated nicotine administration to rats. Nornicotine stimulated DA release from nucleus accumbens in a nicotinic receptor-mediated manner, further supporting the hypothesis that nornicotine contributes to tobacco dependence. Nornicotine is present in Nicotiana tobaccum in both S(-) and R(+) enantiomeric forms. Nornicotine enantiomeric forms appear to differ in analgesic potency and side effects. Exposure to nornicotine results in additional activation of α7-type receptors, which may be important for effects on cognition and attention. Likewise, the effects of nornicotine on α6-containing receptors may contribute to the reinforcing effects of nicotine, and therefore, is relevant to dependence on tobacco. In contrast to nicotine, nornicotine had relatively low activity on receptors other than those containing α7 or α6 subunits. Yaupon Therapeutics was developing Nornicotine as a once a day oral drug for smoking cessation. However this development was discontinued.

Nicotine-1'-N-oxide (NNO) is an oxidation product of nicotine. Flavin-containing monooxygenase is responsible for the oxygen transfer. Nicotine N'- oxide is a primary metabolite of nicotine, although only about 4-7% of nicotine absorbed by smokers is metabolized via this route. It appears that NNO is not further metabolized to any significant extent, except by reduction back to nicotine, which may lead to recycling of nicotine in the body.

(1'R,2'S)-nicotine-1'-N-oxide is a stereoisomer of nicotine-1'-N-oxide, an oxidation product of S-(-)-nicotine. N-1'-oxidation of nicotine is mediated via flavin-containing monooxygenase. A marked stereoselectivity has been observed in the formation of N-1'-oxide metabolites from nicotine. Mammal hepatic preparations generally produce more the N-1'R,2'S-cis diastereoisomer than N-1'S,2'S-trans diastereoisomer after incubation with S-(-)-nicotine. cis- and trans-nicotine-N'-oxides modulate the development of tumors in rats initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.

(1'S,2'S)-nicotine-1'-N-oxide is a stereoisomer of nicotine-1'-N-oxide, an oxidation product of S-(-)-nicotine. N-1'-oxidation of nicotine is mediated via flavin-containing monooxygenase. A marked stereoselectivity has been observed in the formation of N-1'-oxide metabolites from nicotine. Mammal hepatic preparations generally produce more the N-1'R,2'S-cis diastereoisomer than N-1'S,2'S-trans diastereoisomer after incubation with S-(-)-nicotine. (1'S,2'S)-nicotine-1'-N-oxide was reported to bind alpha3beta4 neuronal nicotinic acetylcholine receptor. cis- and trans-nicotine-N'-oxides modulate the development of tumors in rats initiated with N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide.