Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions
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...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2021-10-01
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| Series: | Frontiers in Behavioral Neuroscience |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fnbeh.2021.758252/full |
| _version_ | 1819026223884402688 |
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| author | Xiaoying Tan Kent Vrana Zheng-Ming Ding |
| author_facet | Xiaoying Tan Kent Vrana Zheng-Ming Ding |
| author_sort | Xiaoying Tan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-21T05:23:10Z |
| format | Article |
| id | doaj.art-a0bb4d37b2f944478eddfc3e947f8ca3 |
| institution | Directory Open Access Journal |
| issn | 1662-5153 |
| language | English |
| last_indexed | 2024-12-21T05:23:10Z |
| publishDate | 2021-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Behavioral Neuroscience |
| spelling | doaj.art-a0bb4d37b2f944478eddfc3e947f8ca32022-12-21T19:14:45ZengFrontiers Media S.A.Frontiers in Behavioral Neuroscience1662-51532021-10-011510.3389/fnbeh.2021.758252758252Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its ActionsXiaoying Tan0Kent Vrana1Zheng-Ming Ding2Department of Anesthesiology & Perioperative Medicine, and Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA, United StatesDepartment of Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA, United StatesDepartment of Anesthesiology & Perioperative Medicine, and Pharmacology, Pennsylvania State University College of Medicine, Hershey, PA, United StatesTobacco 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.https://www.frontiersin.org/articles/10.3389/fnbeh.2021.758252/fullbehaviorcotinineneuropharmacologynicotinenicotinic acetylcholine receptor |
| spellingShingle | Xiaoying Tan Kent Vrana Zheng-Ming Ding Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions Frontiers in Behavioral Neuroscience behavior cotinine neuropharmacology nicotine nicotinic acetylcholine receptor |
| title | Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions |
| title_full | Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions |
| title_fullStr | Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions |
| title_full_unstemmed | Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions |
| title_short | Cotinine: Pharmacologically Active Metabolite of Nicotine and Neural Mechanisms for Its Actions |
| title_sort | cotinine pharmacologically active metabolite of nicotine and neural mechanisms for its actions |
| topic | behavior cotinine neuropharmacology nicotine nicotinic acetylcholine receptor |
| url | https://www.frontiersin.org/articles/10.3389/fnbeh.2021.758252/full |
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