Pharmaceuticals
August 15, 2023
Daniel Martins, Eva Gil-Martins, Fernando Cagide et al.
13 citations
Adding an N-2-methoxybenzyl group to mescaline and related 2C phenethylamine drugs to create NBOMe compounds significantly increases their in vitro toxicity to both brain (SH-SY5Y) and liver (HepG2) cell lines. The NBOMe drugs had lower EC50 values, indicating greater potency, and were able to cross the blood–brain barrier. The increased toxicity was linked to higher lipophilicity, disruption of mitochondrial membrane potential, and depletion of glutathione and ATP levels. Inhibition of cytochrome P450 enzymes, particularly CYP3A4 and CYP2D6, influenced the drugs' toxicity, suggesting these enzymes play a role in detoxification or bioactivation. No reactive oxygen species overproduction was detected.
Chemico-biological interactions
April 25, 2025
Eva Gil-Martins, Fernando Cagide, Ana Borer et al.
4 citations
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.
Toxicology reports
June 1, 2025
Eva Gil-Martins, Daniel José Barbosa, Fernanda Borges et al.
2 citations
Psychedelic phenethylamines, including 2C drugs and their NBOMe derivatives, are new psychoactive substances developed to evade drug control regulations. While psychedelics are traditionally considered to have low addiction potential, recent reports raise concerns. These drugs primarily act on serotonin receptors, especially the 5-HT2A subtype, altering perception, mood, and introspection. They are also linked to adverse effects like cardiovascular problems and neurotoxicity. This review examines the psychedelic pathways of 2C and NBOMe drugs, focusing on their interactions with serotonergic and other neurotransmitter systems and their potential for abuse.
Journal of xenobiotics
June 5, 2024
Eva Gil-Martins, Fernando Cagide-Fagín, Daniel Martins et al.
2 citations
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.