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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.
Bassi, Marta; Bilel, Sabrine; Tirri, Micaela; Corli, Giorgia; Di Rosa, Fabiana; Gregori, Adolfo; Alkilany, Alaaldin M; Rachid, Ousama; Roda, Elisa; Zauli, Giorgio; Locatelli, Carlo Alessandro; Marti, Matteo.
Afiliación
  • 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.
Psychopharmacology (Berl) ; 241(3): 489-511, 2024 Mar.
Article en En | MEDLINE | ID: mdl-38214743
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: 5-Metoxitriptamina / Alucinógenos Tipo de estudio: Prognostic_studies Aspecto: Patient_preference Límite: Animals / Humans / Male Idioma: En Revista: Psychopharmacology (Berl) Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: 5-Metoxitriptamina / Alucinógenos Tipo de estudio: Prognostic_studies Aspecto: Patient_preference Límite: Animals / Humans / Male Idioma: En Revista: Psychopharmacology (Berl) Año: 2024 Tipo del documento: Article País de afiliación: Italia Pais de publicación: Alemania