Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions.
Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions.
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DOI：
10.3389/fnbeh.2021.758252
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发表时间：
2021
影响因子：
3
通讯作者：
Ding ZM
中科院分区：
文献类型：
--
作者：
Tan X;Vrana K;Ding ZM
在美国，烟草使用障碍仍然是一个主要的公共卫生问题和导致过早死亡的原因。尼古丁通过作用于烟碱乙酰胆碱受体（nAChRs）被认为是烟草中主要的致瘾生物碱。目前针对尼古丁作用的药物治疗在促进戒烟方面仅产生适度的效果，这突出了对尼古丁成瘾机制的更好理解以告知未来治疗的迫切需要。人们对确定非尼古丁成分对烟草加固的潜在贡献越来越感兴趣。可替宁是一种次要的生物碱，但它是尼古丁的主要代谢物，可以作为nachr的弱激动剂。越来越多的证据表明，可替宁产生多种作用，并可能导致尼古丁的作用。在这篇综述中，我们总结了可替宁作为尼古丁的神经活性代谢物的发现，并讨论了有关其作用的潜在机制的现有证据。临床前研究结果表明，可替宁可穿过血脑屏障，与神经系统中的nachr和非nachr相互作用，并产生神经药理和行为效应。临床研究表明，可替宁对人类有精神活性。然而，回顾有关可替宁的潜在作用机制的证据提供了一个缺乏共识的混合画面。因此，有必要进行更多的研究，以便更好地了解可替宁的作用及其对烟草成瘾的影响。
Tobacco use disorder continues to be a leading public health issue and cause of premature death in the United States. Nicotine is considered as the major tobacco alkaloid causing addiction through its actions on nicotinic acetylcholine receptors (nAChRs). Current pharmacotherapies targeting nicotine’s effects produce only modest effectiveness in promoting cessation, highlighting the critical need for a better understanding of mechanisms of nicotine addiction to inform future treatments. There is growing interest in identifying potential contributions of non-nicotine components to tobacco reinforcement. Cotinine is a minor alkaloid, but the major metabolite of nicotine that can act as a weak agonist of nAChRs. Accumulating evidence indicates that cotinine produces diverse effects and may contribute to effects of nicotine. In this review, we summarize findings implicating cotinine as a neuroactive metabolite of nicotine and discuss available evidence regarding potential mechanisms underlying its effects. Preclinical findings reveal that cotinine crosses the blood brain barrier and interacts with both nAChRs and non-nAChRs in the nervous system, and produces neuropharmacological and behavioral effects. Clinical studies suggest that cotinine is psychoactive in humans. However, reviewing evidence regarding mechanisms underlying effects of cotinine provides a mixed picture with a lack of consensus. Therefore, more research is warranted in order to provide better insight into the actions of cotinine and its contribution to tobacco addiction.
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影响因子：
7
作者：
Boiangiu, Razvan Stefan;Mihasan, Marius;Hritcu, Lucian
通讯作者：
Hritcu, Lucian
影响因子：
6.7
作者：
BENOWITZ, NL;JACOB, P
通讯作者：
JACOB, P
影响因子：
5.8
作者：
BARBIERI, RL;FRIEDMAN, AJ;OSATHANONDH, R
通讯作者：
OSATHANONDH, R
DOI：
10.1124/jpet.108.145292
发表时间：
2009-02-01
影响因子：
3.5
作者：
Buccafusco, Jerry J.;Beach, J. Warren;Terry, Alvin V., Jr.
通讯作者：
Terry, Alvin V., Jr.
影响因子：
8.2
作者：
ABOOD, LG;REYNOLDS, DT;BIDLACK, JM
通讯作者：
BIDLACK, JM