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Neurotoxicity Research

, Volume 35, Issue 4, pp 993–998 | Cite as

25C-NBOMe, a Novel Designer Psychedelic, Induces Neurotoxicity 50 Times More Potent Than Methamphetamine In Vitro

  • Peng Xu
  • Qiyang Qiu
  • Haijie Li
  • Sicheng Yan
  • Mengxiang Yang
  • C. Benjamin Naman
  • Youmei Wang
  • Wenhua Zhou
  • Haowei ShenEmail author
  • Wei CuiEmail author
Brief Communtication

Abstract

25C-NBOMe is a designer substituted phenethylamine and a high-potency psychedelic that acts on the 5-HT2A receptor. Although 25C-NBOMe overdoses have been related to several deaths in the USA and Europe, very limited data exists on the in vitro neurotoxicity of 25C-NBOMe. In this study, we found that 25C-NBOMe potently reduced cell viability of SH-SY5Y, PC12, and SN4741 cells, with IC50 values of 89, 78, and 62 μM, respectively. Methamphetamine decreased the cell viability of these cells with IC50 values at millimolar range in the same tests, indicating that 25C-NBOMe is > 50 times more potent than methamphetamine in its ability to reduce viability of SH-SY5Y cells. The neurotoxicity of 25C-NBOMe on SH-SY5Y cells was further confirmed by using fluorescein diacetate/propidium iodide double staining. 25C-NBOMe elevated the expression of phosphorylated extracellular signal-regulated kinase (pERK), but decreased the expression of phosphorylated Akt and phosphorylated Ser9- glycogen synthase kinase 3β (GSK3β) in time- and concentration-dependent manners. Interestingly, either specific GSK3β inhibitors or specific mitogen-activated protein kinase kinase (MEK) inhibitors significantly prevented 25C-NBOMe-induced neurotoxicity in SH-SY5Y cells. These results suggest that 25C-NBOMe unexpectedly produced more potent neurotoxicity than methamphetamine and that the inhibition of the Akt pathway and activation of the ERK cascade might be involved in 25C-NBOMe-induced neurotoxicity. Most importantly, these findings further inform the toxicity of 25C-NBOMe abuse to the central nervous system for public health.

Keywords

25C-NBOMe Psychedelic Substituted phenethylamine Designer drugs GSK3β ERK 

Notes

Funding

This work was supported by the National Key Research and Development Program of China (2017YFC0803605), the National Natural Science Foundation of China (81673407, 81870853, 81850410553), Ningbo Sci & Tech Project for Common Wealth (2017C50042), Zhejiang Provincial Key Laboratory of Pathophysiology (201804), Ningbo municipal innovation team of life science and health (2015C110026), LiDakSum Marine Biopharmaceutical Development Fund, and the K. C. Wong Magna Fund in Ningbo University.

Supplementary material

12640_2019_12_MOESM1_ESM.docx (147 kb)
ESM 1 (DOCX 146 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Drug Intelligence and Forensic Center, Ministry of Public SecurityBeijingChina
  2. 2.Ningbo Key Laboratory of Behavioral Neuroscience, Zhejiang Provincial Key Laboratory of Pathophysiology, School of MedicineNingbo UniversityNingboChina
  3. 3.Li Dak Sum Yip Yio Chin Kenneth Li Marine Biopharmaceutical Research Center, College of Food and Pharmaceutical SciencesNingbo UniversityNingboChina
  4. 4.Department of Physiology, School of MedicineNingbo UniversityNingboChina

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