Šuláková Anna, Nykodemová Jitka, Palivec Petr, Jurok Radek, Rimpelová Silvie, Leonhardt Tereza, Šíchová Klára, Páleníček Tomáš, Kuchař Martin
Department of Experimental Neurobiology, National Institute of Mental Health, Topolová 748, 250 67 Klecany, Czech Republic.
Forensic Laboratory of Biologically Active Substances, Department of Chemistry of Natural Compounds, University of Chemistry and Technology Prague, Technická 5, 16 628 Prague, Czech Republic.
Metabolites. 2021 Mar 31;11(4):212. doi: 10.3390/metabo11040212.
-Benzylphenethylamines are novel psychedelic substances increasingly used for research, diagnostic, or recreational purposes. To date, only a few metabolism studies have been conducted for -2-methoxybenzylated compounds (NBOMes). Thus, the available 2,5-dimethoxy-4-(2-((2-methoxybenzyl)amino)ethyl)benzonitrile (25CN-NBOMe) metabolism data are limited. Herein, we investigated the metabolic profile of 25CN-NBOMe in vivo in rats and in vitro in () mycelium and human liver microsomes. Phase I and phase II metabolites were first detected in an untargeted screening, followed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) identification of the most abundant metabolites by comparison with in-house synthesized reference materials. The major metabolic pathways described within this study (mono- and demethylation, hydroxylation at different positions, and combinations thereof, followed by the glucuronidation, sulfation, and/or -acetylation of primary metabolites) generally correspond to the results of previously reported metabolism of several other NBOMes. The cyano functional group was either hydrolyzed to the respective amide or carboxylic acid or remained untouched. Differences between species should be taken into account in studies of the metabolism of novel substances.
苄基苯乙胺是新型致幻物质，越来越多地用于研究、诊断或娱乐目的。迄今为止，针对2-甲氧基苄基化化合物（NBOMes）仅开展了少量代谢研究。因此，现有的2,5-二甲氧基-4-(2-((2-甲氧基苄基)氨基)乙基)苯甲腈（25CN-NBOMe）代谢数据有限。在此，我们研究了25CN-NBOMe在大鼠体内以及在（）菌丝体和人肝微粒体中的体外代谢情况。在非靶向筛选中首次检测到I相和II相代谢物，随后通过液相色谱-串联质谱（LC-MS/MS）与内部合成的参考物质进行比较，鉴定出最丰富的代谢物。本研究中描述的主要代谢途径（单甲基化和去甲基化、不同位置的羟基化及其组合，随后是初级代谢物的葡萄糖醛酸化、硫酸化和/或乙酰化）通常与先前报道的其他几种NBOMes的代谢结果相符。氰基官能团要么水解为相应的酰胺或羧酸，要么保持不变。在新物质代谢研究中应考虑物种间的差异。
