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. Author manuscript; available in PMC: 2012 May 16.
Published in final edited form as: Pharmacol Ther. 2009 Apr 8;123(1):1–16. doi: 10.1016/j.pharmthera.2009.03.011

Table 2.

Pharmacotherapy opportunities: new chemical entities and formulations.

Type or class Science base Challenges & opportunities Comment
Lung delivered nicotine Lung delivery is the mode of delivery for most tobacco users. Palatable delivery with an acceptably safe profile for chronic use Achievement of desirable medical goals may result in abuse liability that would warrant controlled substance scheduling.
Nicotine delivery with greater user control over dosing to meet daily and momentary needs Individual dosing needs and needs within the day vary widely and are presently met by tobacco products. Providing flexibility while minimizing risks for user and non-intended users such as children and infants
Diverse nicotinic targeted drugs Cytisine and varenicline have established proof of concept, many more possibilities exist. The range possibilities is vary large, with multiple plausible paths to success. Benefits might be target, e.g., some might be more effective at relieving withdrawal than reducing reinforcing effects of smoking or vice versa.
Non nicotinic drugs, including cannabinoid receptor blockers (e.g., rimonabant-like drugs), and selective dopaminergic inhibitors or agonists Diversity in reasons for tobacco use and withdrawal effects suggests that for some individuals, addressing individual factors will be sufficient to aid withdrawal. Clinical trials may need to be designed with as much emphasis on targeted symptoms as smoking cessation. Indications and claims may differ substantially offering potential “exclusive” markets.
Vaccine type Animal and human studies indicate potential efficacy in reducing reinforcing effects of nicotine and aiding cessation. Depending upon the pharmacological profile of the medications, they may be suited as well if not better for maintaining abstinence and/or aiding tobacco users at early stages of dependence from progressing. Current vaccine development is not pursuing the prophylactic model of immunization of young people but rather as treatment of dependence but that could change. Publically presented data suggest that safety and tolerability issues are manageable and that this category of product is viable within five years.
Antagonists Nicotine antagonists can block nicotine reinforcing effects in humans and animals and alone or in combination with nicotine may aid cessation. A nicotine antagonist with an acceptable profile of effects (e.g., mecamylamine causes a high rate of constipation, dizziness, and sedation) would need to be identified. Whether an acceptable full antagonist can be developed is not clear but selective partial agonist antagonist combinations merit exploration.
Medications approved for other indications Increased understanding of the importance of symptoms of withdrawal and potential factors in self-administration (e.g., stress, anxiety, cognitive dysfunction) suggest that treatment of these symptoms might support smoking cessation. An increasing range of drugs for treating mood and cognitive disorders is available and might be evaluated in paradigms designed to for tobacco withdrawal and dependence. Intellectual property rights and medicinal claims would depend on the approach, status of the drug, and other factors, but this may also be a legitimate way to extend use of existing drugs as occurred with respect to approval of the antidepressant bupropion for smoking cessation.
Pharmacogenetic based approaches Increasing data on genetic differences in nicotine metabolism, addiction risk and treatment needs provide an initial platform for further research. These approaches might be based on existing and forthcoming medications or might involve new chemical entities.