偏向神经素受体信号以阻止精神兴奋剂的滥用
Lauren K Dobbs1, Hitoshi Morikawa1
1Department of Neuroscience and Waggoner Center for Alcohol and Addiction Research, University of Texas at Austin, Austin, TX 78712, USA.
Cell
|May 30, 2020
概括
研究人员开发了一种针对神经素受体的新型偏向性连接体. 这种方法可以减少药物滥用,而不会产生与传统G蛋白信号通路相关的副作用.
科学领域:
- 药理学
- 神经科学
- 药物发现
背景情况:
- 偏向G蛋白合受体 (GPCR) 信号传递是现代药物发现的关键策略.
- 选择性途径激活提供了一种针对特定治疗效果的方法,同时尽量减少不良事件.
- 神经受体系统与各种生理过程有关,包括奖励和成.
研究的目的:
- 报告一种新的β-arrestin偏差的神经受体配体的发展和特征.
- 为了研究这种偏向性连接体在缓解药物滥用行为方面的潜力.
- 评估这种偏向信号方法是否可以避免与正规G蛋白信号相关的副作用.
主要方法:
- 一种针对神经素受体的新型配体的设计和合成.
- 在体外测试以确定途径的选择性 (β-arrestin与G蛋白信号传递).
- 在体内研究以评估联体对药物滥用模型的影响.
主要成果:
- 这种新型连接体在神经素受体上显著偏向于β-arrestin信号传递而不是G蛋白信号传递.
- 在临床前的模型中,β-arrestin偏差的配体显示出降低药物寻找行为的潜力.
- 有证据表明,这种偏向信号方法可以规避通过G蛋白激活神经素受体的常见副作用.
结论:
- 已经成功开发了一种β-arrestin偏差的神经受体配体.
- 这种偏向的连接体代表了治疗物质使用障碍的有前途的治疗策略.
- 针对GPCR的特定信号通路提供了一种精细的药物发现方法,有可能导致更安全,更有效的药物.
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