What We Have Gained from Ibogaine: α3β4 Nicotinic Acetylcholine Receptor Inhibitors as Treatments for Substance Use Disorders,Journal of Medicinal Chemistry

当前位置： X-MOL 学术 › J. Med. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

What We Have Gained from Ibogaine: α3β4 Nicotinic Acetylcholine Receptor Inhibitors as Treatments for Substance Use Disorders
Journal of Medicinal Chemistry ( IF 6.8 ) Pub Date : 2022-11-28 , DOI: 10.1021/acs.jmedchem.2c01562
Carolyn J Straub ₁ , Lisa E Rusali ₁ , Kyle M Kremiller ₁ , Andrew P Riley ₁

Affiliation

For decades, ibogaine─the main psychoactive alkaloid found in Tabernanthe iboga─has been investigated as a possible treatment for substance use disorders (SUDs) due to its purported ability to interrupt the addictive properties of multiple drugs of abuse. Of the numerous pharmacological actions of ibogaine and its derivatives, the inhibition of α3β4 nicotinic acetylcholine receptors (nAChRs), represents a probable mechanism of action for their apparent anti-addictive activity. In this Perspective, we examine several classes of compounds that have been discovered and developed to target α3β4 nAChRs. Specifically, by focusing on compounds that have proven efficacious in pre-clinical models of drug abuse and have been evaluated clinically, we highlight the promising potential of the α3β4 nAChRs as viable targets to treat a wide array of SUDs. Additionally, we discuss the challenges faced by the existing classes of α3β4 nAChR ligands that must be overcome to develop them into therapeutic treatments.

中文翻译：

我们从伊博加因中获得了什么：α3β4 烟碱乙酰胆碱受体抑制剂作为药物使用障碍的治疗方法

几十年来，伊博加因（ Tabernanthe iboga中发现的主要精神活性生物碱）一直被研究作为药物滥用障碍 (SUD) 的可能治疗方法，因为它据称能够中断多种滥用药物的成瘾特性。在伊博加因及其衍生物的众多药理作用中，对 α3β4 烟碱乙酰胆碱受体 (nAChR) 的抑制代表了其明显的抗成瘾活性的可能作用机制。在本视角中，我们研究了几类已发现和开发的针对 α3β4 nAChR 的化合物。具体来说，通过关注已在药物滥用临床前模型中证明有效并经过临床评估的化合物，我们强调了 α3β4 nAChR 作为治疗多种 SUD 的可行靶点的巨大潜力。此外，我们还讨论了现有 α3β4 nAChR 配体类别所面临的挑战，必须克服这些挑战才能将其开发为治疗方法。

更新日期：2022-11-28

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11