Nicotine dependence mechanisms

Cinciripini P, Wetter D, Tomlinson G, Tsoh J, De Moor C, Cinciripini L, Minna J (2004) The effects of the DRD2 polymorphism on smoking cessation and negative affect evidence for a pharmacogenetic effect on mood. Nicotine Tob Res 6 229-239 Clarke PB (1993) Nicotine dependence-mechanisms and therapeutic strategies. Biochem Soc Symp 59 83-95... 

Nortriptyline. Nortriptyhne, a tricychc antidepressant, has been shown in double-blind, placebo-controlled randomized trials to be superior to placebo for smoking cessation (Prochazka et al. 1998). Nortriptyline appears to have efficacy comparable to that of bupropion for smoking cessation (Hall et al. 2002). The efficacy of this agent may be improved with more intensive behavioral therapies (Hall et al. 1998). Nortriptyline s mechanism of action is thought to relate to its noradrenergic and serotonergic reuptake blockade, because these two neurotransmitters have been implicated in the neurobiology of nicotine dependence. Side effects of nortiptyline are typical of tricyclic antidepressants and include dry mouth, blurred vision, constipation, and orthostatic hypotension. Nortriptyline appears to have some utility for smokers with a past history of major depression, and it can be recommended as a second-... 

Dissection of the molecular mechanisms underlying tobacco addiction should lead to new and better treatments to achieve nicotine withdrawal. It seems clear that the dopamine D2 receptor is involved in nicotine dependence and drugs that block this receptor, such as tiapride, could be useful in the treatment of tobacco dependence. Tiapride has been shown to be successful in alcohol withdrawal [58] but would represent a new avenue for tobacco addiction therapy. 

Bafour DJ. (1994). Neural mechanisms underlying nicotine dependence. Addiction. 89(11) 1419-23. Bafour DJ, Benwell ME, Birrell CE, Kelly RJ, Al-Aloul M. (1998). Sensitization of the mesoaccumbens dopamine response to nicotine. Pharmacol Biochem Behav. 59(4) 1021-30. 

Lerman C, Audrain J, Orleans CT, Boyd R, Gold K, Main D, Caporaso N. (1996). Investigation of mechanisms linking depressed mood to nicotine dependence. Addict Behav. 21(1) 9-19. 

Ellers H, Schaeffer E, Bidder PE, Forsayeth JR (1997) Functional deactivation of the major neuronal nicotinic receptor caused by nicotine and a protein kinase C-dependent mechanism. Mol Pharmacol 52 1105-1112... 

Bupropion (Weiibutrin, Zyban). Bupropion is an antidepressant that is also FDA approved as a treatment for smoking cessation. It is marketed as an antidepressant as Weiibutrin and for the treatment of nicotine dependence as Zyban. Its mechanism of action in this regard is obscure, but it may act on dopamine and/or norepinephrine systems. 

Bupropion was approved in 1997 as a treatment for smoking cessation. Approximately twice as many people treated with bupropion as with placebo have a reduced urge to smoke. In addition, patients taking bupropion appear to experience fewer mood symptoms and possibly less weight gain while withdrawing from nicotine dependence. Bupropion appears to be about as effective as nicotine patches in smoking cessation. The mechanism by which bupropion is helpful in this... 

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