Smoking nicotine pharmacology

Rose, J.E., Behm, F.M. Extinguishing the rewarding value of smoke cues pharmacological and behavioral treatments. Nicotine Tob. Res. 6 523, 2004. 

Wesnes K and Warburton DM (1983). Smoking, nicotine and human performance. Pharmacology and Therapeutics, 21, 189-208. 

Lee EW and D Alonzo GE. Cigarette smoking, nicotine addiction and its pharmacological treatment. Arch Intern Med 1993 153 34-48. 

West, R. Si Russell, M. A. H. (1985). Nicotine pharmacology and smoking dependence. In S. D. Iverson (Ed.), Psychopharmacoloyty Recent advances and future prospects303-314). Oxford, LIK Oxford Llnivcrsity Press. 

Cinciprinni PM, McClure JB Smoking cessation recent developments in behavioral and pharmacologic interventions. Oncology 12 249-239, 1998 Clarke PB Nicotinic receptor blockade therapy and smoking cessation. Br J Addict 86 501-503, 1991... 

Hays JT, Hurt RD, Rigotti NA, et al Sustained-release bupropion for pharmacologic relapse prevention after smoking cessation. Ann Intern Med 135 423 33, 2001 Henningfleld JE Nicotine medications for smoking cessation. N Engl J Med 333 1196-1203, 1995... 

Smoking researchers may have to wait for more robust genetic assays before the issue is finally settled [30], but pharmacological inhibitors of CYP2A6 reduce smoking [31] and it seems likely that an inherited defect in nicotine metabolism would have the same effect. 

Nicotine addiction is very complex and pharmacological evidence alongside structure and function analysis of candidate genes may clarify the mechanisms involved. The challenge will be to translate known genetic variation into therapeutic strategies to reduce the prevalence of smoking in the population. 

Alternative pharmacological approaches Clonidine, an o2 adrenergic agonist, has been employed as adjunctive therapy to assist in smoking cessation. However, results have been mixed or the effects small (Gourlay et al. 1994 Hilleman et al. 1993 Franks et al. 1989). Buspirone (BuSpar) is a 5-HTlA partial agonist with anxiolytic effects. It has been tested as a treatment for smoking cessation because anxiety is a prominent feature of nicotine withdrawal (Farid and Abate 1998). To date, results have been mixed and more controlled research is needed. 

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). 

Fig. 2 Blood nicotine concentrations during and after cigarette smoking for 9 min, oral snuff (2.5 g), chewing tobacco (average 7.9 g), and nicotine gum (two 2-mg pieces). Average values for 10 subjects ( SEM). Reprinted from Benowitz et al. (1988) with permission from American Society for Clinical Pharmacology and Therapeutics...

Benowitz NL (1990) Chnical pharmacology of inhaled drags of abuse implications in understanding nicotine dependence. NIDA Res Monogr 99 12-29 Benowitz NL (1996) Cotinine as a biomarker of environmental tobacco smoke exposure. Epidemiol Rev 18(2) 188-204... 

Lobeline has been used in smoking cessation remedies and has been shown to displace nicotine from its binding sites with a Ki of 4 nM, but its pharmacological effects are not typically mediated through a4p2 receptors (Damaj et al. 1997). In drug discrimination, lobeline did not generalise with or block nicotine (Brioni et al. 1994 ReavUl et al. 1990). 

Clark MS, Rand Ml, Vanov S (1965) Comparison of pharmacological activity of nicotine and related alkaloids occurring in cigarette smoke. Arch Int de Pharmacodynamic et de Therapie 156 363-379... 

Rose JE, Behm FM, Westman EC, Bates JE (2003a) Mecamylamine acutely increases human intravenous nicotine self-administration. Pharmacol Biochem Behav 76 307-313 Rose JE, Behm FM, Westman EC, Bates JE, SaUey A (2003b) Pharmacologic and sensorimotor components of satiation in cigarette smoking. Pharmacol Biochem Behav 76 243-250 Rosecrans JA (1979) Nicotine as a discriminative stimulus to behavior its characterization and relevance to smoking behavior. NIDA Res Monogr 23 58-69 Rosecrans JA, Meltzer LT (1981) Central sites and mechanisms of action of nicotine. Neurosci Biobehav Rev 5 497-501... 

Abstract Behavioral discrimination procedures clearly demonstrate that nicotine elicits interoceptive stimulus effects in humans that are malleable by various pharmacological manipulations as well as by some behavioral manipulations. The parameters of nicotine discrimination and both chronic and acute factors that may alter discrimination behavior are addressed in this chapter, which emphasizes research by the author involving nicotine delivered by nasal spray. Human discrimination of nicotine is centrally mediated, as the central and peripheral nicotine antagonist mecamylamine blocks discrimination but the peripheral antagonist trimethaphan does not. The threshold dose for discrimination of nicotine via spray appears to be very low in smokers as well as nonsmokers. Because smoked tobacco delivers nicotine more rapidly than spray, the threshold dose of nicotine via smoking is probably even lower. In terms of individual differences, smokers may become tolerant to the discriminative stimulus effects of higher nicotine doses but not of low doses. 

The goal of these efforts was to ensure that smokers obtained sufficient nicotine to support dependence. Cigarettes were developed and marketed on the premise that the primary motivation for smoking is to obtain the pharmacological effect of nicotine (Philip Morris 1969) and consequently, with the understanding that they must provide the appropriate levels of nicotine (Brown Williamson 1977). 

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