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.

Autor: Bassi M; Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Via Fossato Di Mortara 70, 44121, Ferrara, Italy., Bilel S; Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Via Fossato Di Mortara 70, 44121, Ferrara, Italy., Tirri M; Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Via Fossato Di Mortara 70, 44121, Ferrara, Italy., Corli G; Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Via Fossato Di Mortara 70, 44121, Ferrara, Italy., Di Rosa F; Department of Scientific Investigation (RIS), Carabinieri, 00191, Rome, Italy., Gregori A; Department of Scientific Investigation (RIS), Carabinieri, 00191, Rome, Italy., Alkilany AM; Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha, Qatar., Rachid O; Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Doha, Qatar., Roda E; Laboratory of Clinical & Experimental Toxicology, Pavia Poison Centre, National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Pavia, Italy., Zauli G; Research Department, King Khaled Eye Specialistic Hospital, Riyadh, Saudi Arabia., Locatelli CA; Laboratory of Clinical & Experimental Toxicology, Pavia Poison Centre, National Toxicology Information Centre, Toxicology Unit, Istituti Clinici Scientifici Maugeri, IRCCS, Pavia, Italy., Marti M; Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Via Fossato Di Mortara 70, 44121, Ferrara, Italy. mto@unife.it.; Department of Anti-Drug Policies, Collaborative Center for the Italian National Early Warning System, Presidency of the Council of Ministers, Ferrara, Italy. mto@unife.it.
Jazyk: angličtina
Zdroj: Psychopharmacology [Psychopharmacology (Berl)] 2024 Mar; Vol. 241 (3), pp. 489-511. Date of Electronic Publication: 2024 Jan 12.
DOI: 10.1007/s00213-024-06526-8
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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