评估合成大麻素受体激活剂在大麻素 CB2 受体中的信号偏差
Monica Patel1, Natasha L Grimsey2, Samuel D Banister3,4
1Department of Pharmacology and Toxicology, University of Otago, Dunedin, New Zealand.
Pharmacology research & perspectives
|November 29, 2023
概括
新型合成大麻素受体激动剂 (SCRA) 激活CB2受体,但它们独特的信号配置需要进一步调查公共卫生影响.
科学领域:
- 药理学 药理学是指药理学的学科.
- 毒理学 毒理学 毒理学
- 药物发现 药物发现 药物发现
背景情况:
- 新型合成大麻素受体激动剂 (SCRA) 是新兴的精神活性物质,药理学数据有限.
- 大麻素CB2受体 (CB2) 是理解SCRA活性的一个关键目标.
研究的目的:
- 描述CB2受体上各种SCRA的分子药理学.
- 为了识别CB2信号通路中的潜在联结偏差.
主要方法:
- 在体外测试包括G蛋白激活,ERK1/2酸化和HEK 293细胞中的β-arrestin转位.
- 操作分析以确定带偏差.
- 对SCRAs的测试:4-cyano MPP-BUT7AICA,4F-MDMB-BUTINACA,AMB-FUBINACA,JWH-018,MDMB-4en-PINACA,XLR-11,以及CP55940和THC的参考配体. 这是一个非常好的方法.
主要成果:
- 所有测试的SCRA都激活了CB2信号通路,具体取决于度,具有不同的强度和疗效.
- 检测到具有统计意义的连接物偏差,但化合物活动与参考连接物CP55940.0微妙地不同.
- 与SCRA相比,植物性大麻素THC显示出明显的活性概况,特别是在β-arrestin转位中.
结论:
- CB2受体可以适应结构上多样化的SCRA,从而产生正规的激动剂活性.
- 需要进一步的研究来确定CB2激活是否有助于SCRA毒性.
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