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.