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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

3-CMC: Acute Effects in Male and Female Mice, Human Intoxication Case Series (Italy, 2014–2025), and Prediction of ADMET Properties

by
Marta Bassi
1,
Elisa Roda
2,
Giorgia Corli
1,
Sabrine Bilel
1,
Fabrizio De Luca
3,
Tatiana Bernardi
4,
Adolfo Gregori
5,
Fabiana Di Rosa
6,
Davide Lonati
2,
Carlo Alessandro Locatelli
2 and
Matteo Marti
1,7,*
1
Department of Translational Medicine, Section of Legal Medicine, LTTA Center and University Center of Gender Medicine, University of Ferrara, 44121 Ferrara, Italy
2
Laboratory of Clinical & Experimental Toxicology, Toxicology Unit, Pavia Poison Centre and National Toxicology Information Centre, Istituti Clinici Scientifici Maugeri IRCCS, 27100 Pavia, Italy
3
Department of Biology and Biotechnology “Spallanzani”, University of Pavia, 27100 Pavia, Italy
4
Department of Environmental Sciences and Prevention, University of Ferrara, 44121 Ferrara, Italy
5
Department of Scientific Investigation (RIS), Carabinieri, 00191 Rome, Italy
6
Department of Scientific Investigation (RIS), Carabinieri, 98122 Messina, Italy
7
Collaborative Center for the Italian National Early Warning System (NEWS-D), Department of Anti-Drug Policies and Other Addictions, Presidency of the Council of Ministers, 00186 Rome, Italy
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2025, 26(23), 11600; https://doi.org/10.3390/ijms262311600
Submission received: 13 October 2025 / Revised: 21 November 2025 / Accepted: 26 November 2025 / Published: 29 November 2025
(This article belongs to the Section Molecular Neurobiology)
Versions Notes

Abstract

3-chloromethcathinone (3-CMC) is a synthetic cathinone that gained relevance, having been involved in a large number of seizures and poisoning reports. Despite this, literature currently lacks information on its pharmaco-toxicological effects. This study aims to investigate the acute sensorimotor and physiological effects of 3-CMC (0.1–30 mg/kg; i.p.) in male and female CD-1 mice and its effects (1 and 10 mg/kg) on Prepulse Inhibition (PPI). Furthermore, we describe a series of 3-CMC (or CMC)-related human intoxications (Italy, 2014–2025) registered by the PCC–National Toxicology Information Centre. Finally, we predicted the ADMET properties of 3-CMC compared to 2-CMC, 4-CMC, 2-MMC, and two 3-CMC metabolites. 3-CMC induced in mice locomotor stimulation in mice, relevant tachypnoea and hypothermia, sensorimotor, and PPI alterations were observed only at high doses, with minor sex differences. All intoxications were non-fatal and involved male patients showing psychomotor agitation, psychosis, aggressiveness, CNS depression, but also cardiac arrhythmias, thoracic pain, and tachypnea. N-dealkylation, N-hydroxylation, and phenyl hydroxylation were the main predicted reactions. Drug–drug interaction potential and cardiotoxicity were suggested for all compounds. This interdisciplinary study elucidates 3-CMC effects and its associated risks, opening new objectives for future studies on CMC compounds to provide critical information to clinicians and the toxicological field.
Keywords: 3-CMC; chloro-methcathinones; synthetic cathinones; human intoxications; pharmacokinetic; Novel Psychoactive Substances 3-CMC; chloro-methcathinones; synthetic cathinones; human intoxications; pharmacokinetic; Novel Psychoactive Substances

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MDPI and ACS Style

Bassi, M.; Roda, E.; Corli, G.; Bilel, S.; De Luca, F.; Bernardi, T.; Gregori, A.; Di Rosa, F.; Lonati, D.; Locatelli, C.A.; et al. 3-CMC: Acute Effects in Male and Female Mice, Human Intoxication Case Series (Italy, 2014–2025), and Prediction of ADMET Properties. Int. J. Mol. Sci. 2025, 26, 11600. https://doi.org/10.3390/ijms262311600

AMA Style

Bassi M, Roda E, Corli G, Bilel S, De Luca F, Bernardi T, Gregori A, Di Rosa F, Lonati D, Locatelli CA, et al. 3-CMC: Acute Effects in Male and Female Mice, Human Intoxication Case Series (Italy, 2014–2025), and Prediction of ADMET Properties. International Journal of Molecular Sciences. 2025; 26(23):11600. https://doi.org/10.3390/ijms262311600

Chicago/Turabian Style

Bassi, Marta, Elisa Roda, Giorgia Corli, Sabrine Bilel, Fabrizio De Luca, Tatiana Bernardi, Adolfo Gregori, Fabiana Di Rosa, Davide Lonati, Carlo Alessandro Locatelli, and et al. 2025. "3-CMC: Acute Effects in Male and Female Mice, Human Intoxication Case Series (Italy, 2014–2025), and Prediction of ADMET Properties" International Journal of Molecular Sciences 26, no. 23: 11600. https://doi.org/10.3390/ijms262311600

APA Style

Bassi, M., Roda, E., Corli, G., Bilel, S., De Luca, F., Bernardi, T., Gregori, A., Di Rosa, F., Lonati, D., Locatelli, C. A., & Marti, M. (2025). 3-CMC: Acute Effects in Male and Female Mice, Human Intoxication Case Series (Italy, 2014–2025), and Prediction of ADMET Properties. International Journal of Molecular Sciences, 26(23), 11600. https://doi.org/10.3390/ijms262311600

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