Neutral CB1 Receptor Antagonists as Pharmacotherapies for Substance Use Disorders: Rationale, Evidence, and Challenge.
Neutral CB1 Receptor Antagonists as Pharmacotherapies for Substance Use Disorders: Rationale, Evidence, and Challenge.
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DOI：
10.3390/cells11203262
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发表时间：
2022-10-17
期刊：
影响因子：
6
通讯作者：
Xi, Zheng-Xiong
中科院分区：
文献类型：
--
作者：
Soler-Cedeno, Omar;Xi, Zheng-Xiong
关键词：
大麻素受体1 （Cannabinoid receptor 1, CB1R）已成为药物开发中治疗物质使用障碍（SUDs）的主要靶点之一。早期的研究表明，利莫那班是一种选择性CB1R拮抗剂，具有逆激动剂的特征，作为治疗sud的药物是非常有希望的。然而，它的不良副作用，如抑郁症和自杀，导致它在2008年退出了全球的临床试验。因此，基于认识到利莫那班的副作用可能与其反向激动剂特性有关，许多研究兴趣转向开发中性CB1R拮抗剂。在本文中，我们首先回顾了利莫那班作为一种潜在的药物治疗sud的研究背景。然后，我们讨论了其治疗性抗成瘾作用与不良反应的可能机制。最后，我们讨论了开发中性CB1R拮抗剂作为sud潜在治疗方法的基本原理，最近研究中的支持证据，以及该策略的挑战。我们的结论是，开发无反向激动剂特征的中性CB1R拮抗剂可能是治疗sud的有吸引力的策略。
Cannabinoid receptor 1 (CB1R) has been one of the major targets in medication development for treating substance use disorders (SUDs). Early studies indicated that rimonabant, a selective CB1R antagonist with an inverse agonist profile, was highly promising as a therapeutic for SUDs. However, its adverse side effects, such as depression and suicidality, led to its withdrawal from clinical trials worldwide in 2008. Consequently, much research interest shifted to developing neutral CB1R antagonists based on the recognition that rimonabant’s side effects may be related to its inverse agonist profile. In this article, we first review rimonabant’s research background as a potential pharmacotherapy for SUDs. Then, we discuss the possible mechanisms underlying its therapeutic anti-addictive effects versus its adverse effects. Lastly, we discuss the rationale for developing neutral CB1R antagonists as potential treatments for SUDs, the supporting evidence in recent research, and the challenges of this strategy. We conclude that developing neutral CB1R antagonists without inverse agonist profile may represent attractive strategies for the treatment of SUDs.
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