3-CMC: Acute Effects in Male and Female Mice, Human Intoxication Case Series (Italy, 2014–2025), and Prediction of ADMET Properties
M. Bassi, Elisa Roda, Giorgia Corli, Sabrine Bilel, Fabrizio de Luca, Tatiana Bernardi, Adolfo Gregori, Fabiana di Rosa, Davide Lonati, C. Locatelli, Matteo Marti
International Journal of Molecular Sciences November 29, 2025 DOI: 10.3390/ijms262311600 via OpenAlex
Summary
3-chloromethcathinone (3-CMC), a synthetic cathinone involved in many poisonings, causes locomotor stimulation, rapid breathing, hypothermia, and sensorimotor alterations in mice, with prepulse inhibition changes only at high doses and minor sex differences. All 15 human intoxications in Italy from 2014 to 2025 were non-fatal, involving male patients with psychomotor agitation, psychosis, aggressiveness, CNS depression, cardiac arrhythmias, chest pain, and tachypnea. Predicted metabolic reactions include N-dealkylation, N-hydroxylation, and phenyl hydroxylation, and all compounds show potential for drug-drug interactions and cardiotoxicity.
Study at a glance
| Characteristics | Observational study with experimental animal component and case series Case report Peer reviewed |
|---|---|
| Population | Male and female CD-1 mice; male human patients with 3-CMC intoxication |
| Keywords | Cardiotoxicity Prepulse inhibition Psychomotor learning Acute toxicity Poison control |
| Key finding | 3-CMC induces acute sensorimotor and physiological effects in mice and non-fatal intoxications in humans, with predicted cardiotoxicity and drug-drug interaction potential. |
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.