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
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Published:2024-01-12
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ISSN:0033-3158
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Container-title:Psychopharmacology
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language:en
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Short-container-title:Psychopharmacology
Author:
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 MatteoORCID
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.
Funder
Anti-Drug Policies Department, Presidency of the Council of Ministers, Italy Università degli Studi di Ferrara
Publisher
Springer Science and Business Media LLC
Reference100 articles.
1. Allerta Dronetplus (2016) Triptamine. [Online] Available at: http://allerta.dronetplus.eu/triptamine.html. Accessed 28 July 2023. http://allerta.dronetplus.eu/triptamine.html 2. Altuncı YA, Aydoğdu M, Açıkgöz E, Güven Ü, Düzağaç F, Atasoy A, Dağlıoğlu N, Annette Akgür S (2021) New psychoactive substance 5-MeO-MiPT in vivo acute toxicity and hystotoxicological study. Balkan Med J 38(1):34–42. https://doi.org/10.4274/balkanmedj.galenos.2020.2019.11.68 3. Araújo AM, Carvalho F, MdeL B, Guedes de Pinho P, Carvalho M (2015) The hallucinogenic world of tryptamines: an updated review. Arch Toxicol 89(8):1151–1173. https://doi.org/10.1007/s00204-015-1513-x 4. Arfè R, Bilel S, Tirri M, Corli G, Bergamin E, Serpelloni G, Bassi M, Borsari M, Boccuto F, Bernardi T, Caruso L, Alkilany AM, Rachid O, Botrè F, De-Giorgio F, Marti M (2023) Comprehensive evaluation of the pharmacological and toxicological effects of γ-valerolactone as compared to γ-hydroxybutyric acid: insights from in vivo and in silico models. Drug Alcohol Depend 252:110951. https://doi.org/10.1016/j.drugalcdep.2023.110951 5. Barnes NM, Ahern GP, Becamel C, Bockaert J, Camilleri M, Chaumont-Dubel S, Claeysen S, Cunningham KA, Fone KC, Gershon M, Di Giovanni G, Goodfellow NM, Halberstadt AL, Hartley RM, Hassaine G, Herrick-Davis K, Hovius R, Lacivita E, Lambe EK, Leopoldo M, Levy FO, Lummis SCR, Marin P, Maroteaux L, McCreary AC, Nelson DL, Neumaier JF, Newman-Tancredi A, Nury H, Roberts A, Roth BL, Roumier A, Sanger GJ, Teitler M, Sharp T, Villalón CM, Vogel H, Watts SW, Hoyer D (2021) International Union of Basic and Clinical Pharmacology. CX. Classification of receptors for 5-hydroxytryptamine; pharmacology and function. Pharmacol Rev 73(1):310–520. https://doi.org/10.1124/pr.118.015552
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