Archives of toxicology
March 31, 2026
Kamil Jurowski, Damian Kobylarz, Maciej Noga
Serotonergic tryptamines, including psilocin, psilocybin, DMT, and 5-MeO-DMT, are increasingly used medically and recreationally, but experimental toxicity data are scarce. A comprehensive computational assessment using nine validated QSAR models evaluated six tryptamines for acute toxicity, organ effects, cardiotoxicity, genotoxicity, irritation, and estrogenic activity. All compounds were classified as high toxicological concern (Cramer Class III). Predicted oral LD50 values ranged from 100 to 500 mg/kg, indicating moderate to high acute toxicity. Cardiovascular and gastrointestinal systems were primary targets (≥90% predicted effect). DMT and 5-MeO-DMT showed the highest predicted hERG inhibition (IC50 20–45 µM), suggesting cardiotoxic potential, while psilocybin showed lower risk (IC50 ≈760 µM). Most tryptamines were predicted non-mutagenic and non-endocrine active.
Archives of toxicology
January 28, 2026
Kamil Jurowski, Damian Kobylarz, Maciej Noga
A computational workflow predicted the absorption, distribution, metabolism, and excretion (ADME) profiles of two methoxy-substituted phencyclidine analogues, 3-MeO-PCP and 4-MeO-PCP, for clinical and forensic use. Both analogues are predicted to have high passive permeability, gastrointestinal absorption, and blood-brain barrier access. They are expected to distribute extensively into tissues, with high plasma protein binding (around 70-80%) and large volumes of distribution. Metabolism is primarily by CYP3A4, CYP2D6, and CYP2C19, involving O-demethylation followed by glucuronidation, suggesting potential for drug-drug interactions and genotype effects. 4-MeO-PCP shows a higher theoretical propensity for bioactivation. These predictions guide targeted bioanalysis and matrix selection when in vivo data are limited.
Archives of toxicology
December 8, 2025
Maciej Noga, Kamil Jurowski
Phencyclidine (PCP) and its analogues (3-HO-PCP, 3-MeO-PCP, 4-MeO-PCP, 3-HO-PCE, 3-MeO-PCE, 4-MeO-PCE) are dissociative new psychoactive substances with high abuse potential and limited safety data. An integrated in silico workflow using multiple computational tools predicted moderate acute toxicity for all analogues, with rat oral LD50 values consistently in the 200-630 mg/kg range across platforms, and substantially lower intravenous LD50 values in mice (25-59 mg/kg). Organ-specific predictions highlighted the lungs, liver, and blood as prominent targets, and cardiotoxicity signals included potential hERG inhibition and QT-prolongation risk. Genotoxicity predictions were consistently negative, while eye and skin irritation potential was notable for phenolic analogues. Endocrine screening suggested at most weak-to-moderate estrogen receptor alpha interactions.