News and reviews Pharmacotherapy in smoking cessation: Corticotropin Releasing Factor receptors as emerging intervention targets Ioannis Sotiriou a , Kleanthi Chalkiadaki b , Christos Nikolaidis a , Kyriaki Sidiropoulou b , Ekaterini Chatzaki a, ⁎ a Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis 68100, Greece b Department of Biology, University of Crete, Heraklion 71306, Greece abstract article info Article history: Received 7 September 2016 Received in revised form 13 February 2017 Accepted 13 February 2017 Available online xxxx Smoking represents perhaps the single most important health risk factor and a global contributor to mortality that can unquestionably be prevented. Smoking is responsible for many diseases, including various types of can- cer, chronic obstructive pulmonary disease, coronary heart disease, peripheral vascular disease and peptic ulcer, while it adversely affects fetal formation and development. Since smoking habit duration is a critical factor for mortality, the goal of treatment should be its timely cessation and relapse prevention. Drug intervention therapy is an important ally in smoking cessation. Significant positive steps have been achieved in the last few years in the development of supportive compounds. In the present review, we analyze reports studying the role of Corticotro- pin Releasing Factor (CRF), the principle neuroendocrine mediator of the stress response and its two receptors (CRF1 and CRF2) in the withdrawal phase as well as in the abstinence from nicotine use. Although still in pre-clin- ical evaluation, therapeutic implications of these data were investigated in order to highlight potential pharma- ceutical interventions. © 2017 Published by Elsevier Ltd. Keywords: Corticotropin Releasing Factor Receptor Nicotine Smoking cessation Pharmacotherapy Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 2. Nicotine and its actions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3. Current pharmacotherapeutic approaches in smoking cessation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.1. Nicotine replacement therapy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.2. Bupropion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.3. Varenicline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.4. Notriptyline . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.5. Clonidine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.6. Rimonabant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 3.7. Immunization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4. The CRF system of neuropeptides and receptors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4.1. CRF and withdrawal neurocircuits . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4.2. Actions of CRF on nicotine abstinence, withdrawal and relapse . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4.3. CRF actions in metabolism during withdrawal . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4.4. Pharmacological agents acting as CRF1 receptor antagonists . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4.5. CRF actions in behavioral modification in specific groups . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 4.6. CRF actions in the brain reward system. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0 Neuropeptides xxx (2017) xxx–xxx ⁎ Corresponding author at: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. E-mail address: achatzak@med.duth.gr (E. Chatzaki). YNPEP-01793; No of Pages 9 http://dx.doi.org/10.1016/j.npep.2017.02.082 0143-4179/© 2017 Published by Elsevier Ltd. Contents lists available at ScienceDirect Neuropeptides journal homepage: www.elsevier.com/locate/npep Please cite this article as: Sotiriou, I., et al., Pharmacotherapy in smoking cessation: Corticotropin Releasing Factor receptors as emerging intervention targets, Neuropeptides (2017), http://dx.doi.org/10.1016/j.npep.2017.02.082