运动运动刺激作用的结构-活性关系和替代安非他命和加丁的单胺转运体相互作用
Lauren R Fitzgerald1, Brenda M Gannon1, Donna Walther2
1Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR, 72205, USA.
Neuropharmacology
|December 28, 2023
概括
这项研究揭示了乙胺的化学修饰,如对或β-的添加,如何影响它们的兴奋剂效果和输送活性. 了解这些结构-活性关系对于预测新型精神活性物质的风险至关重要.
科学领域:
- 药理学 药理学是指药理学的学科.
- 神经科学是一个神经科学.
- 药用化学 医学化学
背景情况:
- 来自乙胺结构的新型精神活性物质 (NPS),包括安非他和甲基,构成越来越多的公共卫生挑战.
- 了解结构修改的药理学影响是预测新兴药物的行为关键.
研究的目的:
- 为了建立结构-活性关系 (SAR) 对于12种乙烯胺的运动运动刺激剂和单胺转运体效应,使用各种替代物.
- 调查对,β-基,N-甲基和N-乙基添加剂对乙胺药理学的影响.
主要方法:
- 用自动光束分析评估小鼠的运动运动活动.
- 在体外测试中,使用大鼠大脑突触体确定了化合物在多巴胺 (DAT),北上腺素 (NET) 和血清素 (SERT) 载体上的活性.
主要成果:
- 所有测试的化合物,除了4-chloro-N-ethylcathinone,刺激了小鼠的运动.
- 胺类药物是比它们的β-类类似物更强大的兴奋剂;对替代剂增加了疗效和诱导死亡率.
- 化合物抑制了DAT,NET和SERT的吸收,通常作为释放剂. 副和N-乙烯替代物改变了输送器的强度和释放能力.
结论:
- 对于发动机刺激,单胺转运体活性和乙烯胺的致死性,已证明有序的结构-活性关系.
- 替代化合物在小鼠中表现出显著的毒性,这表明人类休使用者的潜在严重风险.
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