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.
Int J Mol Sci
March 26, 2025
Eva Gil-Martins, Daniel José Barbosa, Fernando Cagide et al.
Sublethal concentrations of the designer drugs 2C-I and 25I-NBOMe impair development and reproductive behavior in the roundworm Caenorhabditis elegans. Exposed worms showed delayed growth and altered egg-laying patterns, indicating that even low, non-lethal doses of these substances can disrupt key biological processes. The findings suggest potential developmental and reproductive risks from these drugs.
Applied Sciences Switzerland
February 1, 2024
Daniel Martins, Carlos Fernandes, Ricardo F. Mendes et al.
A molecularly imprinted polymer (MIP) was developed to selectively recognize the psychedelic compound 2C-B. Using 2C-B as a template and methacrylic acid as the functional monomer in a 1:4 ratio, microwave-assisted polymerization produced a material with a maximum absorption capacity of 115.6 μmol·mg−1 and a dissociation constant (Kd) of 26.7 μM. The imprint factor was 4.2 compared to a non-imprinted polymer, and the material showed good selectivity against 14 other new psychoactive substances. This MIP may aid in monitoring non-medical use of 2C-B and in therapeutic models involving psychedelics.