New medications development for smoking cessation

Abstract

Diseases associated with nicotine dependence in the form of habitual tobacco use are a major cause of premature death in the United States. The majority of tobacco smokers will relapse within the first month of attempted abstinence. Smoking cessation agents increase the likelihood that smokers can achieve long-term abstinence. Nevertheless, currently available smoking cessation agents have limited utility and fail to prevent relapse in the majority of smokers. Pharmacotherapy is therefore an effective strategy to aid smoking cessation efforts but considerable risk of relapse persists even when the most efficacious medications currently available are used. The past decade has seen major breakthroughs in our understanding of the molecular, cellular, and systems-level actions of nicotine in the brain that contribute to the development and maintenance of habitual tobacco use. In parallel, large-scale human genetics studies have revealed allelic variants that influence vulnerability to tobacco use disorder. These advances have revealed targets for the development of novel smoking cessation agents. Here, we summarize current efforts to develop smoking cessation therapeutics and highlight opportunities for future efforts.

Fig. 1.

Summary of factors that influence vulnerability to tobacco use disorder and opportunities for new medications development. GABA, ϒ-aminobutyric acid; Hcrt1, hypocretin receptor 1; IPN, interpeduncular nucleus; MAO-B, monoamine oxidase B; mGluR; metabotropic glutamate receptor; MHb, medial habenula; MOR, mu opioid receptor; nAChR, nicotinic acetylcholine receptor; NAM, negative allosteric modulator; PAM, positive allosteric modulator; PPAR, peroxisome-proliferator-activated receptor.