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Purpose. The neurobiology of tobacco dependence and the efficacy and safety of emerging pharmacotherapies for smoking cessation are reviewed.
Summary. Dopamine is pivotal to the major addictive properties of nicotine. The neurotransmitters that influence dopamine activity include γ-aminobutyric acid, acetylcholine, glutamate, norepinephrine, and serotonin. Opioids and endocannabinoids can also affect dopamine activity. Research on pharmacologic treatments for nicotine dependence has targeted the modulation of these neurotransmitter systems. Current pharmacotherapies for smoking cessation include bupropion and varenicline, both of which target the neurotransmitters involved in nicotine addiction. Several new therapies are emerging as possible treatment options for smoking cessation. Rimonabant, a selective cannabinoid antagonist, blocks dopamine release in the nucleus accumbens, a primary reward center for the brain. Studies have found that rimonabant may not only be effective as a smoking-cessation aid but may also assist in the maintenance of nicotine abstinence. Rimonabant has also demonstrated a weight-loss benefit, which may be attractive to smokers concerned with weight gain associated with smoking cessation. Three nicotine vaccines are currently in development, each acting to sequester nicotine from the bloodstream, thereby preventing its penetration of the central nervous system. Ongoing studies will evaluate their use as established therapies for smoking cessation. New nicotine-replacement formulations are also being developed.
Conclusion. There are several promising products in development targeting the mechanisms of tobacco dependence. As failure rates are high and relapse is common, these emerging therapies would offer more therapeutic options for smoking cessation and solutions to the problem of relapse.
- Autonomic drugs
- Mechanism of action
- Nicotine vaccines
- Nicotinic agonists
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