利苏里德和lysergic 酸二甲基胺的药理学效应对比重重审视
Grant C Glatfelter1, Eline Pottie2, John S Partilla1
1Designer Drug Research Unit, National Institute on Drug Abuse, Intramural Research Program, Baltimore, Maryland 21224, United States.
利苏里德是一种非幻化类型的血清素 (5-HT) 2A受体激动剂,由于其在血清素1A受体 (5-HT1A) 的强大活性,因此缺乏幻化效应. 这种双重作用解释了为什么利苏里德与LSD不同,不会产生迷幻效应.
科学领域:
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
- 心理药理学 心理药理学
背景情况:
- 利苏里德是一种血清素 (5-HT) 2A受体激动剂,也是lysergic acid diethylamide (LSD) 的类似物.
- 利苏里德还作为一种血清素1A受体 (5-HT1A) 激动剂,这种特性可以抵消迷幻效应.
- 利苏里德缺乏迷幻活性背后的机制需要进一步研究.
研究的目的:
- 调查利苏里德缺乏迷幻活性是由于5-HT2A受体的部分激动作用和5-HT1A受体的强烈激动作用.
- 为了比较lisuride和LSD对5-HT2A和5-HT1A信号传导的体外和体内效应.
主要方法:
- 使用miniGαq和β-arrestin 2招募试验对5-HT2A信号的lysuride,LSD和类似物进行体外表征.
- 在体内比较5-HT1A和5-HT2A介导的利苏里德和LSD在雄性C57BL/6J小鼠的影响.
- 评估头部抽反应 (HTRs),低温和低运动.
主要成果:
- 在体外,LSD是一种强大的5-HT2A激动剂,而利苏里德显示部分疗效和对抗LSD.
- 在小鼠中,LSD诱导了HTRs,而利苏里德抑制了HTRs,并产生了低温和低运动,这些效应被5-HT1A对手阻止.
- 利苏里德在小鼠中表现出超强的5-HT1A激动作用,限制了其作为5-HT2A连接体在急性药物效应研究中的实用性.
结论:
- 利苏里德在5-HT2A受体上的部分激动-对抗活性,结合其强大的5-HT1A激动,解释了其缺乏迷幻效应.
- 这些发现突出了lisuride复杂的药理学及其在特定研究环境中作为工具化合物的潜力.
- 利苏里德在小鼠中的强烈5-HT1A活性需要在解释其对5-HT2A介导行为的影响时仔细考虑.
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