Return of the lysergamides. Part II: Analytical and behavioural characterization of N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2′S,4′S)-lysergic acid 2,4-dimethylazetidide (LSZ)
Return of the lysergamides. Part II: Analytical and behavioural characterization of N6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2′S,4′S)-lysergic acid 2,4-dimethylazetidide (LSZ)
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DOI：
10.1002/dta.1985
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发表时间：
2017-01-01
影响因子：
2.9
通讯作者：
Halberstadt, Adam L.
中科院分区：
文献类型：
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作者：
Brandt, Simon D.;Kavanagh, Pierce V.;Halberstadt, Adam L.
麦角酸N，N-二乙基酰胺（LSD）可能是已知的最有趣的精神活性物质之一，在过去的几十年里，许多类似物已经在不同程度上被探索。2013年，n -6-烯丙基-6-去甲麦角酸二乙胺（AL-LAD）和(2' s,4'S)-麦角酸2,4-二甲基肼（LSZ）以粉末状和吸附剂形式出现在研究化学品/新型精神活性物质（NPS）市场。本文报道了AL-LAD和LSZ酒石酸盐粉状样品的分析表征及其在吸墨纸上的半定量测定。本研究包括核磁共振（NMR）光谱、气相色谱-质谱（GC-MS）、低质量精度和高质量精度电喷雾质谱（/MS）、高效液相色谱二极管阵列检测和GC固态红外分析。5-羟色胺类致幻剂（如LSD）的一个共同特征是能够通过激活5-HT2A受体来调节行为反应。在雄性C57BL/6J小鼠中，AL-LAD和LSZ均表现出lsd样反应。AL-LAD和LSZ产生几乎相同的倒u型剂量依赖性效应，最大反应发生在200 μ g/kg时。非线性回归的剂量效应分析证实，LSZ （ED50=114.2nmol/kg）与LSD （ED50=132.8nmol/kg）对小鼠具有相当的作用，而AL-LAD的作用稍弱（ED50=174.9nmol/kg）。效力比较在多大程度上可以直接应用于人类，需要进一步调查。从NPS获得的化学和药理学数据可以帮助研究团体对与物质使用和法医鉴定有关的各个方面感兴趣。版权所有：John Wiley & Sons， Ltd。
Lysergic acid N,N-diethylamide (LSD) is perhaps one of the most intriguing psychoactive substances known and numerous analogs have been explored to varying extents in previous decades. In 2013, N-6-allyl-6-norlysergic acid diethylamide (AL-LAD) and (2'S,4'S)-lysergic acid 2,4-dimethylazetidide (LSZ) appeared on the research chemicals'/new psychoactive substances (NPS) market in both powdered and blotter form. This study reports the analytical characterization of powdered AL-LAD and LSZ tartrate samples and their semi-quantitative determination on blotter paper. Included in this study was the use of nuclear magnetic resonance (NMR) spectroscopy, gas chromatography-mass spectrometry (GC-MS), low and high mass accuracy electrospray MS(/MS), high performance liquid chromatography diode array detection and GC solid-state infrared analysis. One feature shared by serotonergic psychedelics, such as LSD, is the ability to mediate behavioural responses via activation of 5-HT2A receptors. Both AL-LAD and LSZ displayed LSD-like responses in male C57BL/6J mice when employing the head-twitch response (HTR) assay. AL-LAD and LSZ produced nearly identical inverted-U-shaped dose-dependent effects, with the maximal responses occurring at 200 mu g/kg. Analysis of the dose responses by nonlinear regression confirmed that LSZ (ED50=114.2nmol/kg) was equipotent to LSD (ED50=132.8nmol/kg) in mice, whereas AL-LAD was slightly less potent (ED50=174.9nmol/kg). The extent to which a comparison in potency can be translated directly to humans requires further investigation. Chemical and pharmacological data obtained from NPS may assist research communities that are interested in various aspects related to substance use and forensic identification. Copyright (c) 2016 John Wiley & Sons, Ltd.