Smoking cessation 3: nicotinic partial agonists in smoking cessation – varenicline and cytisine

2009 ◽  
Vol 2 (2) ◽  
pp. 87
Author(s):  
Paul Aveyard ◽  
Amanda Parsons ◽  
Rachna Begh
2007 ◽  
Vol 28 (7) ◽  
pp. 316-325 ◽  
Author(s):  
Hans Rollema ◽  
Jotham W. Coe ◽  
Leslie K. Chambers ◽  
Raymond S. Hurst ◽  
Stephen M. Stahl ◽  
...  

2018 ◽  
Vol 16 (4) ◽  
pp. 19-32
Author(s):  
Elena V. Radchenko ◽  
Olga A. Sykhovskaya ◽  
Timofey L. Galankin ◽  
Aleksei S. Kolbin ◽  
Maria A. Smirnova

Background. Partial agonists of α4b2 nicotinic acetylcholine receptors are the most effective treatment strategy for tobacco smoking cessation. They are able to alleviate withdrawal symptoms and to reduce smoking satisfaction. The aim of this study was to review the efficacy and safety of nicotinic receptor partial agonists varenicline and cytisine, for smoking cessation. Methods. A search for randomized controlled trials was done using the terms (“cytisine”, “tabex”, “varenicline” or 'partial agonists of nicotinic receptors’) in MEDLINE, EMBASE, eLibrary in May 2018. Types of participants, the doses and duration of the treatments, efficacy and safety parameters, quality of randomization and blinding procedures were evaluated. Bayesian network meta-analysis was performed. Results. Cytisine overcame placebo in the 12, 24 and 52 weeks of therapy with the following odds ratios (ORs) for abstinence: 3.3 (95% CrI 1.8–5.8), 3.9 (2.4–6.7), 3.8 (CrI 1.3–11,9) accordingly. Varenicline in 2 mg/day dose overcame placebo in the 12, 24 and 52 weeks of therapy with the ORs: 4.0 (3.3–4.7), 3.1 (2.5–3.7), 2.9 (2.2–4.1) accor dingly. Varenicline in 1 mg/day dose overcame placebo in 12 and 52 weeks of therapy, the ORs were 3.0 (2.0–4.7) and 2.3 (1.3–4.4) accordingly. Varenicline in 0.5 mg/day dose overcame placebo in 12 weeks of therapy only with the OR 2.4 (1.3–4.4). Cytisine and varenicline 2 mg/day were associated with more gastrointestinal disturbances than placebo with the ORs 6.2 (2.1–22.8) and 2.4 (2.0–2.8) accordingly. Cytisine and varenicline 2 mg/day were associated with more psychiatric problems than placebo with ORs 5.2 (1.9–15.1) and 1.6 (1.3–1.9) accordingly. There was no difference in serious adverse events between the investigated drugs and placebo: OR for cytisine was 2.4 (0.8–6.8), varenicline 0.5 mg/day – 2.0 (0.5–6.6), varenicline 1.0 mg/day – 1.0 (0.3–2.7), varenicline 2 mg/day – 1.0 (0.7–1.4). Conclusion. Cytisine was proved to be as effective and safe aid for smoking cessation as varenicline.


2021 ◽  
Author(s):  
Aaron L. Nichols ◽  
Zack Blumenfeld ◽  
Chengcheng Fan ◽  
Laura Luebbert ◽  
Annet E. M. Blom ◽  
...  

ABSTRACTNicotinic partial agonists provide an accepted aid for smoking cessation and thus contribute to decreasing tobacco-related disease. Improved drugs constitute a continued area of study. However, there remains no reductionist method to examine the cellular and subcellular pharmacokinetic properties of these compounds in living cells. Here, we developed new intensity-based drug sensing fluorescent reporters (“iDrugSnFRs”) for the nicotinic partial agonists dianicline, cytisine, and two cytisine derivatives – 10-fluorocytisine and 9-bromo-10-ethylcytisine. We report the first atomic-scale structures of liganded periplasmic binding protein-based biosensors, accelerating development of iDrugSnFRs and also explaining the activation mechanism. The nicotinic iDrugSnFRs detect their drug partners in solution, as well as at the plasma membrane (PM) and in the endoplasmic reticulum (ER) of cell lines and mouse hippocampal neurons. At the PM, the speed of solution changes limits the growth and decay rates of the fluorescence response in almost all cases. In contrast, we found that rates of membrane crossing differ among these nicotinic drugs by > 30 fold. The new nicotinic iDrugSnFRs, in combination with previously described nicotine and varenicline sensors, provide insight into the real-time pharmacokinetic properties of nicotinic agonists and provide a methodology whereby iDrugSnFRs can inform both pharmaceutical neuroscience and addiction neuroscience.


2012 ◽  
Vol 130 (5) ◽  
pp. 346-347 ◽  
Author(s):  
Kate Cahill ◽  
Lindsay F. Stead ◽  
Tim Lancaster ◽  
Igor Bastos Polonio

eLife ◽  
2022 ◽  
Vol 11 ◽  
Author(s):  
Aaron L Nichols ◽  
Zack Blumenfeld ◽  
Chengcheng Fan ◽  
Laura Luebbert ◽  
Annet EM Blom ◽  
...  

Nicotinic partial agonists provide an accepted aid for smoking cessation and thus contribute to decreasing tobacco-related disease. Improved drugs constitute a continued area of study. However, there remains no reductionist method to examine the cellular and subcellular pharmacokinetic properties of these compounds in living cells. Here, we developed new intensity-based drug sensing fluorescent reporters ('iDrugSnFRs') for the nicotinic partial agonists dianicline, cytisine, and two cytisine derivatives - 10-fluorocytisine and 9-bromo-10-ethylcytisine. We report the first atomic-scale structures of liganded periplasmic binding protein-based biosensors, accelerating development of iDrugSnFRs and also explaining the activation mechanism. The nicotinic iDrugSnFRs detect their drug partners in solution, as well as at the plasma membrane (PM) and in the endoplasmic reticulum (ER) of cell lines and mouse hippocampal neurons. At the PM, the speed of solution changes limits the growth and decay rates of the fluorescence response in almost all cases. In contrast, we found that rates of membrane crossing differ among these nicotinic drugs by > 30 fold. The new nicotinic iDrugSnFRs provide insight into the real-time pharmacokinetic properties of nicotinic agonists and provide a methodology whereby iDrugSnFRs can inform both pharmaceutical neuroscience and addiction neuroscience.


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