Translational Toxicology of N-Isopropylbutylone: Integrated In Vivo and In Silico Assessment of a New Synthetic Cathinone
5 affiliations
- 1Department of Translational Medicine, Section of Legal Medicine, LTTA Center and University Center of Gender Medicine, University of Ferrara, 44121 Ferrara, Italy
- 2Department of Environmental Sciences and Prevention, University of Ferrara, 44121 Ferrara, Italy
- 3Department of Chemical, Pharmaceutical and Agricultural Sciences, University of Ferrara, 44121 Ferrara, Italy
- 4Forensic Toxicology Laboratory, Department of Healthcare Surveillance and Bioethics, Università Cattolica del Sacro Cuore F. Policlinico Gemelli IRCCS, 00168 Rome, Italy
- 5Collaborative Center for the Italian National Early Warning System (NEWS-D), Department of Anti-Drug Policies and Other Addictions, Presidency of the Council of Ministers, 00184 Rome, Italy
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.
Related
- Synthetic Cannabinoids: Metabolism, Biomarkers of Exposure and Advanced Analytical Strategies in Forensic and Clinical Toxicology
- Integrated transcriptomics and network toxicology suggests core targets and potential mechanisms of aspartame-related breast carcinogenesis
- 6PPDQ Promotes Cutaneous Squamous Cell Carcinoma Growth with PI3K-Akt/MMP9 Activation: Evidence from Integrated Network Toxicology and Experimental Investigation
- Environmental PFOA exposure and the risk of metabolic dysfunction-associated steatotic liver disease: An integrated computational toxicology and multi-omics study
- Synergistic effects of combined exposure to hydroquinone and nitrofurantoin in T24 bladder cells: an in vitro toxicology study with implications for risk assessment.
BibTeX
@article{bassi2026translational,
title = {{Translational Toxicology of N-Isopropylbutylone: Integrated In Vivo and In Silico Assessment of a New Synthetic Cathinone}},
author = {Marta Bassi and Sabrine Bilel and Giorgia Corli and Nicole Cocita and Asia Masoli and Tatiana Bernardi and Sara Odoardi and Serena Mestria and Giulia Biosa and Sabina Strano-Rossi and Matteo Marti},
journal = {International journal of molecular sciences},
year = {2026},
month = sep,
doi = {10.3390/ijms27198795},
url = {https://europepmc.org/article/PMC/PMC13665128},
note = {CC BY},
}
RIS
TY - JOUR
TI - Translational Toxicology of N-Isopropylbutylone: Integrated In Vivo and In Silico Assessment of a New Synthetic Cathinone
AU - Marta Bassi
AU - Sabrine Bilel
AU - Giorgia Corli
AU - Nicole Cocita
AU - Asia Masoli
AU - Tatiana Bernardi
AU - Sara Odoardi
AU - Serena Mestria
AU - Giulia Biosa
AU - Sabina Strano-Rossi
AU - Matteo Marti
PY - 2026
DA - 2026/09/30
JO - International journal of molecular sciences
DO - 10.3390/ijms27198795
UR - https://europepmc.org/article/PMC/PMC13665128
AB - 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.
SN - 1422-0067
ER -