Associate Laboratory i4HB-Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal; UCIBIO-Applied Molecular Biosciences Unit, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313, Porto, Portugal.
2 papers in the library · 6 citations · publishing 2024-2025
25I-NBOMe is significantly more cytotoxic than 2C-I in differentiated SH-SY5Y cells and primary rat cortical cultures, likely due to its higher lipophilicity. Both drugs cause severe mitochondrial dysfunction, including decreased ATP levels and mitochondrial membrane depolarization, without significant changes in reactive oxygen or nitrogen species. 25I-NBOMe also elevates intracellular calcium levels. Apoptosis occurs with both drugs, but 2C-I additionally induces autophagy and strong caspase-3 activation, suggesting caspase-3-dependent apoptosis, while 25I-NBOMe may trigger caspase-3-independent apoptosis through calcium dysregulation and direct mitochondrial damage. Mitochondrial dysfunction and calcium dysregulation are central to the neurotoxicity of these NPS.
Substituted phenethylamines, including 2C and NBOMe drugs, are potent psychoactive substances with unknown toxicity. In laboratory experiments using rat brain cells and a human cell line, six such drugs (2C-T-2, 2C-T-4, 2C-T-7 and their NBOMe versions) caused concentration-dependent cell death. NBOMe drugs were more toxic than their 2C counterparts, a difference linked to their lipophilicity. The cell damage involved mitochondrial dysfunction, shown by loss of mitochondrial membrane potential and lower ATP levels. Two drugs, 2C-T-7 and 25T7-NBOMe, also disrupted calcium regulation. Although reactive oxygen species did not increase, total glutathione levels fell, indicating oxidative stress. These findings clarify the mechanisms behind these drugs' neurotoxicity.