Pharmaco-toxicological effects of the novel tryptamine hallucinogen 5-MeO-MiPT on motor, sensorimotor, physiological, and cardiorespiratory parameters in mice—from a human poisoning case to the preclinical evidence

Psychopharmacology · 12 authors, 6 centres

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TL;DR

This preclinical study in mice found that 5-MeO-MiPT dose-dependently inhibits sensorimotor and sensory gating responses and, at high doses, impairs motor activity and causes cardiorespiratory changes.

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The study used CD-1 male mice to characterize the acute effects of systemic administration (0.01–30 mg/kg i.p.) of the novel psychedelic 5-MeO-MiPT. High doses (30 mg/kg) impaired motor coordination and induced cardiorespiratory alterations. The findings suggest the compound's effects could impair daily activities and pose health risks, particularly at high doses or in combination with other substances, but its therapeutic potential for psychiatric disorders warrants further exploration.

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other

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preclinical research

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ORIGINAL PAPER

PMC10884077

Pharmaco-toxicological effects of the novel tryptamine hallucinogen 5-MeO-MiPT on motor, sensorimotor, physiological, and cardiorespiratory parameters in mice—from a human poisoning case to the preclinical evidence

Psychopharmacology

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ABSTRACT

Abstract Rationale The 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT, known online as “Moxy”) is a new psychedelic tryptamine first identified on Italian national territory in 2014. Its hallucinogen effects are broadly well-known; however, only few information is available regarding its pharmaco-toxicological effects. Objectives Following the seizure of this new psychoactive substances by the Arm of Carabinieri and the occurrence of a human intoxication case, in the current study we had the aim to characterize the in vivo acute effects of systemic administration of 5-MeO-MiPT (0.01–30 mg/kg i.p.) on sensorimotor (visual, acoustic, and overall tactile) responses, thermoregulation, and stimulated motor activity (drag and accelerod test) in CD-1 male mice. We also evaluated variation on sensory gating (PPI, prepulse inhibition; 0.01–10 mg/kg i.p.) and on cardiorespiratory parameters (MouseOx and BP-2000; 30 mg/kg i.p.). Lastly, we investigated the in silico ADMET (absorption, distribution, metabolism, excretion, toxicity) profile of 5-MeO-MiPT compared to 5-methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT) and N,N-dimethyltryptamine (DMT). Results This study demonstrates that 5-MeO-MiPT dose-dependently inhibits sensorimotor and PPI responses and, at high doses, induces impairment of the stimulated motor activity and cardiorespiratory changes in mice. In silico prediction shows that the 5-MeO-MiPT toxicokinetic profile shares similarities with 5-MeO-DIPT and DMT and highlights a cytochrome risk associated with this compound. Conclusions Consumption of 5-MeO-MiPT can affect the ability to perform activities and pose a risk to human health status, as the correspondence between the effects induced in mice and the symptoms occurred in the intoxication case suggests. However, our findings suggest that 5-MeO-MiPT should not be excluded from research in the psychiatric therapy field. Keywords: 5-MeO-MiPT, Human intoxication, Serotoninergic hallucinogens, Behaviour, Cardiorespiratory changes, Prepulse inhibition, ADMET prediction

CITATION EXPORT

Marta Bassi, Sabrine Bilel, Micaela Tirri et al.. Pharmaco-toxicological effects of the novel tryptamine hallucinogen 5-MeO-MiPT on motor, sensorimotor, physiological, and cardiorespiratory parameters in mice—from a human poisoning case to the preclinical evidence. Psychopharmacology. (2024). https://doi.org/10.1007/s00213-024-06526-8

AUTHORS

12 · 6 CENTRES

Marta Bassi, Sabrine Bilel, Micaela Tirri, Giorgia Corli, Fabiana Di Rosa, Adolfo Gregori, Alaaldin M Alkilany, Ousama Rachid, Elisa Roda, Giorgio Zauli, Carlo Alessandro Locatelli, Matteo Marti

1Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Via Fossato Di Mortara 70, 44121 Ferrara, Italy
2Department of Scientific Investigation (RIS), Carabinieri, 00191 Rome, Italy
3Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha, Qatar
4Laboratory of Clinical & Experimental Toxicology, Pavia Poison Centre, National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Pavia, Italy
5Research Department, King Khaled Eye Specialistic Hospital, Riyadh, Saudi Arabia
6Department of Anti-Drug Policies, Collaborative Center for the Italian National Early Warning System, Presidency of the Council of Ministers, Ferrara, Italy