International Journal of Legal Medicine
May 1, 2019
Hyewon Seo, In Sook Kim, Young-Hoon Kim et al.
9 citations
The synthetic psychoactive substance 25N-NBOMe, a phenethylamine, was metabolized in vitro using human liver microsomes. Fourteen metabolites (M1–M14) were identified through liquid chromatography-quadrupole time-of-flight mass spectrometry. The biotransformations included hydroxylation, O-demethylation, N-dealkylation, nitro reduction, dehydrogenation, and carbonylation. The hydroxyl metabolite was the most abundant after phase I metabolism. These findings offer potential biomarkers for detecting 25N-NBOMe ingestion.
Pharmacology, biochemistry, and behavior
February 1, 2022
Jin Mook Kim, Boreum Han, Hyun Kyu Min et al.
4 citations
Deschloroketamine (10 mg/kg) and diphenidine (10-60 mg/kg) produced increased locomotor activation and stereotypy similar to ketamine (10 mg/kg) in mice. Both substances increased preference for the drug-paired compartment in conditioned place preference testing, indicating rewarding effects. In self-administration tests, deschloroketamine (1 mg/kg/infusion) increased active lever presses and infusions, suggesting reinforcing effects, whereas diphenidine (1, 2 mg/kg/infusion) did not alter these measures. Both compounds increased dopamine levels in PC-12 cells. The data suggest deschloroketamine may have both rewarding and reinforcing effects, while diphenidine only induced rewarding effects.
International Journal of Legal Medicine
July 1, 2021
Young-Ki Hong, Young-Hoon Kim, Jin-Moo Lee et al.
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.
Drug and chemical toxicology (New York, N.Y. 1978)
June 29, 2020
K. S. Yoon, Sun Mi Gu, Hye Jin Cha et al.
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.
Toxicology Letters
November 6, 2019
K. S. Yoon, Jin-Moo Lee, Young-Hoon Kim et al.
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.
Toxicology Letters
April 1, 2019
K. S. Yoon, Jaesuk Yun, Young-Hoon Kim et al.
Two 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.