2-(2,5-Dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)ethanamine (25D-NBOMe) and N-(2-methoxybenzyl)-2,5-dimethoxy-4-chlorophenethylamine (25C-NBOMe) induce adverse cardiac effects in vitro and in vivo.
K. S. Yoon, Jaesuk Yun, Young-Hoon Kim, Jisoon Shin, Sung Jin Kim, Jungwon Seo, Sung-Ae Hyun, S. Suh, Hye Jin Cha
Toxicology Letters April 1, 2019 DOI: 10.1016/j.toxlet.2019.01.004 (opens in new tab) via Semantic Scholar
Summary
AI-generated from the abstractTwo emerging psychoactive substances, 25D-NBOMe and 25C-NBOMe, show potential for disrupting heart rhythm, based on laboratory and animal tests. At 100 μM, both compounds reduced cell viability in a cell-based assay. In rats, doses of 2.0 mg/kg and 0.75 mg/kg prolonged QT intervals on electrocardiography, a marker of altered cardiac repolarization. The compounds also decreased levels of PAK1, a protein linked to cardiotoxicity, and 25D-NBOMe inhibited potassium channels in a hERG assay. The findings suggest these substances may pose a risk for cardiac arrhythmias, but further research is needed to clarify the role of PAK1 down-regulation.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rat |
| Interventions | 25D-NBOMe 25C-NBOMe |
| Dose | 100 μM, 2.0 mg/kg, 0.75 mg/kg |
| Keywords | Medicine Chemistry |
| Key finding | Both 25D-NBOMe and 25C-NBOMe have potential cardiotoxicity, especially regarding cardiac rhythm, as shown by reduced cell viability, prolonged QT intervals in rat ECG, PAK1 down-regulation, and potassium channel inhibition. |
Abstract
Two emerging psychoactive substances, 2-(2,5-dimethoxy-4-methylphenyl)-N-(2-methoxybenzyl)ethanamine (25D-NBOMe) and N-(2-methoxybenzyl)-2,5-dimethoxy-4-chlorophenethylamine (25C-NBOMe), are being abused, leading to fatal and non-fatal intoxications. However, most of their adverse effects have been reported anecdotally. In the present study, cardiotoxicity was evaluated through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, rat electrocardiography (ECG), and human ether-a-go-go-related gene (hERG) assay. Expression levels of p21 (CDC42/RAC)-activated kinase 1 (PAK1), one of known biomarkers for cardiotoxicity, were also analyzed. Both 25D-NBOMe and 25C-NBOMe at 100 μM reduced cell viability in MTT assay. At 2.0 mg/kg and 0.75 mg/kg, they prolonged QT intervals in rat ECG. PAK1 was down-regulated by treatment with these two test compounds. Furthermore, potassium channels were inhibited by 25D-NBOMe treatment in hERG assay. Taken together, these results suggest that both 25D-NBOMe and 25C-NBOMe have potential cardiotoxicity, especially regarding cardiac rhythm. Further studies are needed to confirm the relationship between PAK1 down-regulation and cardiotoxicity.