Grafinger Katharina Elisabeth, Wilke Andreas, König Stefan, Weinmann Wolfgang
Institute of Forensic Medicine, Forensic Toxicology and Chemistry, University of Bern, Bühlstrasse 20, 3012, Bern, Switzerland.
Graduate School for Cellular and Biomedical Sciences, University of Bern, Freiestrasse 1, 3012, Bern, Switzerland.
Drug Test Anal. 2019 May;11(5):721-729. doi: 10.1002/dta.2544. Epub 2018 Dec 25.
Tryptamines can occur naturally in plants, mushrooms, microbes, and amphibians. Synthetic tryptamines are sold as new psychoactive substances (NPS) because of their hallucinogenic effects. When it comes to NPS, metabolism studies are of crucial importance, due to the lack of pharmacological and toxicological data. Different approaches can be taken to study in vitro and in vivo metabolism of xenobiotica. The zygomycete fungus Cunninghamella elegans (C. elegans) can be used as a microbial model for the study of drug metabolism. The current study investigated the biotransformation of four naturally occurring and synthetic tryptamines [N,N-Dimethyltryptamine (DMT), 4-hydroxy-N-methyl-N-ethyltryptamine (4-HO-MET), N,N-di allyl-5-methoxy tryptamine (5-MeO-DALT) and 5-methoxy-N-methyl-N-isoporpoyltryptamine (5-MeO-MiPT)] in C. elegans after incubation for 72 hours. Metabolites were identified using liquid chromatography-high resolution-tandem mass spectrometry (LC-HR-MS/MS) with a quadrupole time-of-flight (QqTOF) instrument. Results were compared to already published data on these substances. C. elegans was capable of producing all major biotransformation steps: hydroxylation, N-oxide formation, carboxylation, deamination, and demethylation. On average 63% of phase I metabolites found in the literature could also be detected in C. elegans. Additionally, metabolites specific for C. elegans were identified. Therefore, C. elegans is a suitable complementary model to other in vitro or in vivo methods to study the metabolism of naturally occurring or synthetic tryptamines.
色胺可天然存在于植物、蘑菇、微生物和两栖动物中。合成色胺因其致幻作用而作为新型精神活性物质（NPS）出售。对于新型精神活性物质而言，由于缺乏药理学和毒理学数据，代谢研究至关重要。可以采用不同方法来研究外源性物质的体外和体内代谢。接合菌真菌秀丽隐杆线虫（C. elegans）可作为研究药物代谢的微生物模型。本研究调查了四种天然存在和合成的色胺 [N,N-二甲基色胺（DMT）、4-羟基-N-甲基-N-乙基色胺（4-HO-MET）、N,N-二烯丙基-5-甲氧基色胺（5-MeO-DALT）和 5-甲氧基-N-甲基-N-异丙烯基色胺（5-MeO-MiPT）] 在秀丽隐杆线虫中孵育 72 小时后的生物转化情况。使用配备四极杆飞行时间（QqTOF）仪器的液相色谱 - 高分辨率 - 串联质谱（LC-HR-MS/MS）鉴定代谢产物。将结果与已发表的关于这些物质的数据进行比较。秀丽隐杆线虫能够产生所有主要的生物转化步骤：羟基化、N-氧化物形成、羧化、脱氨和去甲基化。文献中发现的 I 相代谢产物平均有 63% 也能在秀丽隐杆线虫中检测到。此外，还鉴定出了秀丽隐杆线虫特有的代谢产物。因此，秀丽隐杆线虫是研究天然存在或合成色胺代谢的一种合适的补充模型，可与其他体外或体内方法互补。
