Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo, São Paulo, Brazil.
School of Pharmaceutical Science, University of São Paulo, São Paulo, Brazil.
Basic Clin Pharmacol Toxicol. 2018 Mar;122(3):305-309. doi: 10.1111/bcpt.12913. Epub 2017 Oct 18.
Varenicline is a synthetic chemical substance produced from the alkaloid cytisine, used for smoking treatment, which acts as a partial agonist for α4β2 and α3β4 nicotinic cholinergic receptors and as a total agonist for α7 receptor. While there are studies regarding varenicline's non-smoking-related effects, as in treatment for drug dependence, there are no studies in the literature evaluating the long-term toxicity of varenicline through a physiological approach. Thus, the aim of this study was to evaluate possible toxicity through haematological, biochemical and anatomopathological parameters of prolonged exposure (30 days) to varenicline in rats. Three doses of varenicline were used: 0.03 (therapeutic dose for human beings), 0.1 and 0.3 mg/kg orally (gavage). Body-weight, water and food intake were measured weekly during treatment. On the 30th treatment day, blood and various organs were collected for haematological, biochemical and anatomopathological evaluations. The results show a decrease in some biochemical parameters in animals from the 0.1 and 0.3 mg/kg group, although the values are within the normal range of the species. There were no changes in the other evaluations performed. Together, these data indicate that prolonged exposure of rats to different doses of varenicline was not able to alter haematological, biochemical and anatomopathological parameters.
伐伦克林是一种从毒蕈碱 Cytisine 中提取的合成化学物质，用于治疗吸烟，作为α4β2 和α3β4 烟碱型乙酰胆碱受体的部分激动剂，以及α7 受体的完全激动剂。虽然有关于伐伦克林与吸烟无关的作用的研究，如治疗药物依赖，但没有文献评估通过生理方法长期暴露于伐伦克林的长期毒性。因此，本研究旨在通过延长暴露（30 天）至大鼠的伐伦克林的血液学、生化和解剖病理学参数来评估可能的毒性。使用了三种伐伦克林剂量：0.03（人类的治疗剂量）、0.1 和 0.3mg/kg 口服（灌胃）。在治疗期间每周测量体重、水和食物摄入量。在第 30 天治疗日，收集血液和各种器官进行血液学、生化和解剖病理学评估。结果显示，0.1 和 0.3mg/kg 组的一些生化参数下降，尽管这些值仍在该物种的正常范围内。其他评估没有变化。总之，这些数据表明，延长暴露于不同剂量的伐伦克林对大鼠的血液学、生化和解剖病理学参数没有改变。
