Two new psychoactive substances, 25I-NBOH and 25C-NBOH, abused as recreational hallucinogens, were evaluated for cardiotoxicity. In cell and animal tests, both compounds decreased viability of rat heart cells and prolonged QT and RR intervals in rat electrocardiography, indicating potential heart rhythm disturbances. 25I-NBOH reduced PAK1 protein expression in heart cells and inhibited potassium channels in a hERG assay, while 25C-NBOH did not affect PAK1 expression. Neither substance altered the pumping function or heart rate of isolated rat hearts. The findings suggest both substances may pose cardiovascular risks, with further research needed on the role of PAK1.
Methamnetamine (PAL-1046), an amphetamine-based new psychoactive substance that causes excessive serotonin release, is not regulated in most countries and had no prior metabolism studies. Using human liver microsomes and flavin-containing monooxygenase analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry, eight phase I metabolites were identified. Metabolic processes include N-demethylation, N-hydroxylation, and aromatic hydroxylation. N-hydroxylated metabolites were confirmed using expressed FMOs. The major metabolite results from hydroxylation of the naphthalene ring. These findings may help detect methamnetamine ingestion by users.
The psychoactive substance 25I-NBOMe, a phenethylamine analog, is toxic to heart muscle cells and can disrupt normal heart electrical activity in rats. In laboratory tests, the compound reduced the viability of rat heart cells in a dose-dependent manner, with a half-maximal toxic concentration of 70.4 μM. It also lowered the activity of the protein PAK1, which plays a key role in cardiovascular function. When injected into rats at doses of 1.0 and 3.0 mg/kg, 25I-NBOMe prolonged the QTc interval on electrocardiograms, an abnormal pattern linked to risk of dangerous heart rhythms. The findings suggest that 25I-NBOMe's cardiotoxicity involves PAK1-related pathways.
Two synthetic tryptamines, 4-AcO-DET and 4-HO-MET, are abused as recreational hallucinogens and may pose unknown health risks. In laboratory tests, both substances increased the proliferation of rat heart cells in a concentration-dependent manner, prolonged QT intervals in rats, and inhibited potassium channels in hamster cells, indicating potential cardiotoxicity. Expression of the PAK1 protein, involved in cardiovascular function, did not change. The findings suggest these new psychoactive substances could cause adverse cardiovascular effects, supporting evidence for their legal scheduling.