PUBLICATION
Metabolism study of two phenethylamine - derived new psychoactive substances using in silico, in vivo, and in vitro approaches
- Authors
- Tang, Y., Xu, L., Guo, Z., Zhao, J., Xiao, Y., Xiang, P., Xu, L., Yan, H.
- ID
- ZDB-PUB-250311-15
- Date
- 2025
- Source
- Archives of toxicology : (Journal)
- Registered Authors
- Keywords
- Human liver microsome, In silico prediction, Metabolism, Zebrafish, phenethylamine
- MeSH Terms
-
- Animals
- Computer Simulation
- Humans
- Microsomes, Liver/drug effects
- Microsomes, Liver/metabolism
- Phenethylamines*/chemistry
- Phenethylamines*/metabolism
- Psychotropic Drugs*/chemistry
- Psychotropic Drugs*/metabolism
- Zebrafish/metabolism
- PubMed
- 40064698 Full text @ Arch. Toxicol.
Citation
Tang, Y., Xu, L., Guo, Z., Zhao, J., Xiao, Y., Xiang, P., Xu, L., Yan, H. (2025) Metabolism study of two phenethylamine - derived new psychoactive substances using in silico, in vivo, and in vitro approaches. Archives of toxicology. :.
Abstract
New psychoactive substances (NPS) are substances that are not controlled by international drug control conventions but are abused and pose a threat to public health. Proscaline and methallylescaline are two phenylethylamines with psychoactive and stimulant effects and are also derivatives of the classic hallucinogen mescaline. However, limited toxicity information on proscaline and methallylescaline has hindered the identification of these two NPS. Therefore, data on the metabolic profiles of proscaline and methallylescaline are urgently needed. In this study, high-resolution mass spectrometry was used to establish three complementary metabolism models-computational prediction (in silico), zebrafish (in vivo), and human liver microsomes (in vitro)-to study the in vivo and in vitro metabolic fates of proscaline and methallylescaline. The models provided the first identification of 7 proscaline metabolites and 11 methallylescaline metabolites. In addition, hydroxylated and N-acetylated products were identified as the major metabolites of these two phenylethylamines. This enabled the selection of hydroxylated and N-acetylated metabolites as biomarkers of proscaline and methallylescaline, thereby facilitating the specific detection of the intake of these two NPSs in a relatively wide detection window.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping