在小鼠中的ADB-BICA,ADB-BINACA,ADB-4en-PINACA和MDMB-4en-PINACA的不同类大麻素效应和药理动力学:一项比较研究
Fenghua Zhou1, Xiaoli Wang1, Sujun Tan1
1College of Forensic Medicine, Hebei Medical University, Hebei Key Laboratory of Forensic Medicine, Collaborative Innovation Center of Forensic Medical Molecular Identification, Research Unit of Digestive Tract Microecosystem Pharmacology and Toxicology, Chinese Academy of Medical Sciences, Shijiazhuang, Hebei Province, China.
Addiction biology
|February 21, 2024
概括
测试了四种合成大麻素对小鼠的影响. MDMB-4en-PINACA显示出最强的效果,而ADB-BICA则没有. 了解这些药物特征是安全的关键.
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
- 神经科学是一个神经科学.
背景情况:
- 合成大麻素 (SCs) 越来越普遍,但缺乏全面的数据.
- 新的SCs的快速出现使理解它们的影响变得复杂.
- 这项研究研究了四个特定的SCs:ADB-BICA,ADB-BINACA,ADB-4en-PINACA和MDMB-4en-PINACA.
研究的目的:
- 区分四个SCs的药理学和药理动力学概况.
- 确定影响它们对运动活动,体温和感觉的因果因素.
- 了解SCs与大麻素受体1 (CB1R) 的分子相互作用.
主要方法:
- 成年雄性C57BL/6小鼠接受了四种SC的不同剂量 (0.020.5 mg/kg) 的腹腔内注射.
- 测量了运动活动,体温和感觉值.
- 进行了分子结合配置和LC-MS/MS分析.
- 用CB1R抗剂AM251来评估受体参与.
主要成果:
- ADB-BINACA,ADB-4en-PINACA和MDMB-4en-PINACA诱导的剂量和时间依赖的低温和低温效应.
- 在0.1mg/kg的剂量下,MDMB-4en-PINACA表现出显著的止痛特性.
- ADB-BICA没有显示出明显的效应.
- MDMB-4en-PINACA显示出最强大和持续的效果,具有最长的等离子检测窗口.
- 分子分析揭示了一致的结合几何结构,并确定了CB1R中的关键残留物 (PHE268,PHE200,SER173),这些残留物对SC相互作用至关重要.
结论:
- MDMB-4en-PINACA和ADB-4en-PINACA是强大的合成大麻素,具有显著的药理作用.
- 在测试剂量下,ADB-BICA似乎在药理上是无活性的.
- 了解SC药理学和药理动力学对于临床解释和风险评估至关重要.
- 鉴定的结合相互作用为SCs在CB1R中的作用机制提供了洞察力.
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