Grizzell J Alex, Echeverria Valentina
Department of Psychiatry and Behavioral Neurosciences, Morsani College of Medicine, University of South Florida, Tampa, FL, 33611, USA.
Department of Research and Development, Bay Pines VA Healthcare System, 10,000 Bay Pines Blvd., Bldg. 23, Rm. 123, Bay Pines, FL, 33744, USA.
Neurochem Res. 2015 Oct;40(10):2032-46. doi: 10.1007/s11064-014-1359-2. Epub 2014 Jun 27.
Tobacco consumption is far higher among a number of psychiatric and neurological diseases, supporting the notion that some component(s) of tobacco may underlie the oft-reported reduction in associated symptoms during tobacco use. Popular dogma holds that this component is nicotine. However, increasing evidence support theories that cotinine, the main metabolite of nicotine, may underlie at least some of nicotine's actions in the nervous system, apart from its adverse cardiovascular and habit forming effects. Though similarities exist, disparate and even antagonizing actions between cotinine and nicotine have been described both in terms of behavior and physiology, underscoring the need to further characterize this potentially therapeutic compound. Cotinine has been shown to be psychoactive in humans and animals, facilitating memory, cognition, executive function, and emotional responding. Furthermore, recent research shows that cotinine acts as an antidepressant and reduces cognitive-impairment associated with disease and stress-induced dysfunction. Despite these promising findings, continued focus on this potentially safe alternative to tobacco and nicotine use is lacking. Here, we review the effects of cotinine, including comparisons with nicotine, and discuss potential mechanisms of cotinine-specific actions in the central nervous system which are, to date, still being elucidated.
在一些精神疾病和神经疾病患者中，烟草消费量要高得多，这支持了一种观点，即烟草的某些成分可能是烟草使用期间相关症状经常出现减轻现象的原因。普遍的看法认为这种成分是尼古丁。然而，越来越多的证据支持这样的理论，即可替宁作为尼古丁的主要代谢产物，可能是尼古丁在神经系统中至少某些作用的基础，这与其不良的心血管效应和成瘾作用无关。尽管可替宁和尼古丁之间存在相似之处，但二者在行为和生理方面都存在不同甚至相互拮抗的作用，这突出表明需要进一步研究这种具有潜在治疗作用的化合物。可替宁已被证明在人和动物中具有精神活性，可促进记忆、认知、执行功能和情绪反应。此外，最近的研究表明，可替宁具有抗抑郁作用，并可减轻与疾病和应激诱导的功能障碍相关的认知损害。尽管有这些令人鼓舞的发现，但目前仍缺乏对这种潜在安全的烟草和尼古丁替代品的持续关注。在此，我们综述了可替宁的作用，包括与尼古丁的比较，并讨论了可替宁在中枢神经系统中特定作用的潜在机制，迄今为止，这些机制仍有待阐明。
