Ecotoxicology and Environmental Safety
January 31, 2024
Sen Zhao, Jinyuan Chen, Chenhao Zhong et al.
3 citations
5-MeO-MiPT, a novel psychoactive tryptamine, caused inhibited movement and anxiety-like behavior in adult zebrafish. Metabolomic analysis after drug injection revealed 22 distinct potential biomarkers and seven significantly altered metabolic pathways, including amino acid, lipid, and energy metabolism. The metabolic changes indicated observable brain damage, especially disruption in the liver-brain pathway, linking the drug's metabolic effects to the anxiety-like behavior.
Ecotoxicology and Environmental Safety
August 30, 2024
Sen Zhao, Meng Liu, Jinyuan Chen et al.
1 citation
5-Methoxy-N-isopropyl-N-methyltryptamine (5-MeO-MiPT), a tryptamine-derived novel psychoactive substance detected in aquatic environments, alters gene expression and disrupts signaling pathways in zebrafish. After 30 days of injection with varying concentrations, RNA-seq, qPCR, metabolomics, and histopathology showed that 5-MeO-MiPT significantly affects the transcription of 13 genes, including ucp1, pet100, grik3, and grik4, via the Gα q/11-PLCβ signaling pathway. The substance inhibits DAG-Ca2+/Pkc/Erk, Pkc/Pla2/PLCs, and Ca2+/CamkII/NMDA pathways while enhancing Ca2+/Creb, mechanisms that may mediate behavioral inhibition and oxidative stress. These findings clarify toxicological and addiction mechanisms of 5-MeO-MiPT and suggest approaches for studying other tryptamine-based NPS and diagnosing liver-brain pathway diseases.
Journal of pharmaceutical and biomedical analysis
April 15, 2024
Yanjiao Wang, Chenhao Zhong, Jinyuan Chen et al.
5-MeO-MiPT is metabolized through multiple phase I and II pathways in both zebrafish and human liver microsomes. In zebrafish, six metabolites were identified, with N-Demethylation and Indole-hydroxylation as primary phase I reactions, and Glucoside conjugation and Sulfonation as phase II reactions. In human liver microsomes, nine metabolites were generated, including N-Demethylation, 5-O-Demethylation, N-Depropylation, N-Oxidation, Indole-hydroxylation, and combined reactions. Phase II metabolism in human microsomes involved Glucoside conjugation after Indole-hydroxylation or 5-O-Demethylation. Proposed markers for screening 5-MeO-MiPT intake include 5-MeO-MiPT-N-Demethylation, 5-MeO-MiPT-Indole-hydroxylation, and OH&Glucoside conjugation-5-MeO-MiPT, along with the parent drug.