Translational Toxicology of N-Isopropylbutylone: Integrated In Vivo and In Silico Assessment of a New Synthetic Cathinone
Marta Bassi, Sabrine Bilel, Giorgia Corli, Nicole Cocita, Asia Masoli, Tatiana Bernardi, Sara Odoardi, Serena Mestria, Giulia Biosa, Sabina Strano-Rossi, Matteo Marti
International Journal of Molecular Sciences September 30, 2026 DOI: 10.3390/ijms27198795 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical animal study with in silico pharmacokinetic modelling Peer reviewed |
|---|---|
| Population | Male mice |
| Intervention | N-isopropyl butylone (NiPB) |
| Dose | 0.1–60 mg/kg; i.p. |
| Key points | In male mice, NiPB (0.1–60 mg/kg i.p.) produced dose-dependent locomotor stimulation without affecting motor coordination, along with tachypnoea and visual reflex alterations, while tactile and acoustic responses and thermoregulation were preserved. Computational modelling predicted high blood-brain barrier permeability, hERG blockade (pIC50 = 4.888), and CYP2D6 and OCT2 inhibition, leading the authors to conclude that acute exposure may trigger central psychostimulant toxicity and that cardiotoxicity and drug–drug interaction risks require targeted study. |
Abstract
The novel psychoactive substance (NPS) phenomenon represents a major global problem. Despite the methodical inclusion of new analogues in lists of controlled drugs, new compounds continue to circulate, frequently resulting in fatal intoxications. The emergence of N-isopropyl butylone (NiPB) in 2024, found as an adulterant in methamphetamine-based products, underscores the rapidly evolving landscape of NPSs. Despite its structural similarity to potent monoamine transporter inhibitors, specific pharmacological data and information on its effects in consumers are currently lacking. This study aims to characterize the acute physiological, behavioural, and sensorimotor effects of NiPB (0.1–60 mg/kg; i.p.) in male mice, complemented by in silico pharmacokinetic modelling (ADMET Predictor®). NiPB is predicted to undergo N-dealkylation, cleavage of the 3,4-methylendioxy moiety, and N-glucuronidation. Computational profiling predicted high BBB permeability, Vd = 4.37 L/kg, fup > 50%, CYP2D6 and OCT2 inhibition, and hERG blockade (pIC50 = 4.888). In vivo, NiPB induced dose-dependent locomotor stimulation without affecting motor coordination and provoked tachypnoea and visual reflex alterations, while tactile and acoustic responses, as well as thermoregulation, were preserved. In conclusion, this study defines the preliminary toxicological profile of NiPB, indicating that acute exposure may trigger central psychostimulant toxicity in vivo. Furthermore, based on the in silico profiling, targeted experimental studies are required to determine the actual cardiotoxicity and risks of drug–drug interactions associated with NiPB.