Pharmacology of nicotine

Zevin S, Gourlay SG and Benowitz NL (1998). Clinical pharmacology of nicotine. Clinics in Dermatology, 16, 557-564. 

An illustration of the variable responses to nicotine concerns aphids. In an experiment, 2 per cent of an insect population died or became moribund when exposed to 0.0001 M nicotine solution, 48 per cent were affected when the concentration was 0.0025 M, and 98.5 per cent when the concentration was 0.012 M. The concentrations of nicotine required to affect all the insects alike varied more than 120-fold.21 The pharmacology of nicotine as studied in mammals is notably complex and unpredictable, partly because many sites of action are involved. Its effect on different human individuals is also diverse, but it has not been adequately investigated, particularly in view of the fairly well established fact that amblyopia and Buerger s disease occur in relatively rare cases directly because of its use.22... 

Damaj MI, Creasy KR, Welch SP, Rosecrans JA, Aceto MD, Martin BR. (1995). Comparative pharmacology of nicotine and ABT-418, a new nicotinic agonist. Psychopharmacoiogy (Berlin). 

An understanding of the pharmacology of nicotine and how nicotine produces addiction and influences smoking behavior provides a necessary basis for therapeutic advances in smoking cessation interventions. This chapter provides a review of several aspects of the human pharmacology of nicotine. These include the presence and levels of nicotine and related alkaloids in tobacco products, the absorption of nicotine from tobacco products and nicotine medications, the distribution of nicotine in body tissues, the metabolism and renal excretion of nicotine, nicotine and cotinine blood levels during tobacco use or nicotine replacement therapy, and biomarkers of nicotine exposure. For more details and references on the pharmacokinetics and metabolism of nicotine, the reader is referred to Hukkanen et al. (2005c). 

Nicotine is extensively metabolized to a nnmber of metabolites (Fig. 3) by the liver. Six primary metabolites of nicotine have been identified. Qnantitatively, the most important metabolite of nicotine in most mammalian species is the lactam derivative, cotinine. In humans, about 70-80% of nicotine is converted to cotinine. This transformation involves two steps. The first is mediated primarily by CYP2A6 to produce nicotine-A -iminium ion, which is in equilibrium with 5 -hydroxynicotine. The second step is catalyzed by a cytoplasmic aldehyde oxidase. Nicotine iminiiim ion has received considerable interest since it is an alkylating agent and, as such, could play a role in the pharmacology of nicotine (Shigenaga etal. 1988). 

Stolerman IP (1999) Inter-species consistency in the behavioural pharmacology of nicotine dependence, Behav Pharmacol 10 559-580... 

Stewart J (1983) Conditioned and unconditioned drug effects in relapse to opiate and stimulant drug-administration. Prog Neuropsychopharmacol Biol Psychiatry 7 591-597 Stolerman IP (1988) Characterization of central nicotinic receptors by studies on the nicotine cue and conditioned taste aversion in rats. Pharmacol Biochem Behav 30 235-242 Stolerman IP (1989) Discriminative stimulus effects of nicotine in rats trained under different schedules of reinforcement. Psychopharmacology 97 131-138 Stolerman IP (1999) Inter-species consistency in the behavioural pharmacology of nicotine dependence. Behav Pharmacol 10 559-580... 

Balfour DJK, Fagerstrom KO, Pharmacology of nicotine and its therapeutic use in smoking cessation and neurodegenerative disorders, Pharmacol Ther 72 51-81, 1996. 

Benowitz NL Pharmacology of nicotine Addiction, smoking-induced disease, and therapeutics. Annu Rev Pharmacol Toxicol 2008 Oct. 3 [Epub ahead of print],... 

FIGURE 13-18. Pharmacology of nicotine (part 1). Nicotine acts directly on nicotinic cholinergic receptors, which are themselves located in part on mesolimbic dopamine neurons. When nicotine stimulates these receptors (A and B), it causes release of dopamine from the mesolimbic neurons and thereby conveys a sense of reward and pleasure. 

The West Discovers Tobacco Tobacco as Panacea From Panacea to Panned Prevalence of Tobacco Use Smoking in the United States Initiation of Smoking Smokeless Tobacco Use Pharmacology of Nicotine Sites of Action Pharmacokinetics Tolerance and Dependence Tolerance... 

This chapter considers individual differences in the pharmacology of nicotine. While there is evidence of genetic difference in pharmacologic response to nicotine in rodents (Marks et al. 1991), there has been very little research into individual differences in pharmacodynamics in humans. Individual differences in pharmacokinetics and metabolism have been much better documented, and are the major focus of this discussion. 

Compiled from data of Holmstedt B (1988). In Rand MJ and Thurau K (eds.) The Pharmacology of Nicotine. IRL Press, Oxford Washington DC, pp. 61-88. 

Hoffmann, D., J.D. Adams, E.J. LaVoie, and S.S. Hecht Biochemistry, pharmacokinetics and carcinogenicity of nicotine-derived nitrosamines in The pharmacology of nicotine, edited by M.J. Rand and K. Thurau, Washington, DC (1988) 43-60. 

Approximately 40-60 mg of nicotine (43) is a lethal dose for an adult human the LD50 i.v. in mouse is 0.3 mg/kg (Wink, 1993). This base is the main pharmacologically active component of tobacco smoke and probably is responsible for the addictive nature of cigarettes. The pharmacology of nicotine and other Nicotiana alkaloids has been reviewed (Fodor and Colasanti, 1985). Nicotine mimics acetylcholine and activates acetylcholine receptors (Wink, 1993). 

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