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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| Title: | 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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| Authors: | Bassi, Marta (AUTHOR), Bilel, Sabrine (AUTHOR), Tirri, Micaela (AUTHOR), Corli, Giorgia (AUTHOR), Di Rosa, Fabiana (AUTHOR), Gregori, Adolfo (AUTHOR), Alkilany, Alaaldin M. (AUTHOR), Rachid, Ousama (AUTHOR), Roda, Elisa (AUTHOR), Zauli, Giorgio (AUTHOR), Locatelli, Carlo Alessandro (AUTHOR), Marti, Matteo (AUTHOR) |
| Source: | Psychopharmacology. Mar2024, Vol. 241 Issue 3, p489-511. 23p. |
| Subjects: | Tryptamine, Neural inhibition, Hallucinogenic drugs, Poisoning, Psilocybin, Mice |
| 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. [ABSTRACT FROM AUTHOR] |
| Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.) | |
| Database: | Psychology and Behavioral Sciences Collection |
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| Header | DbId: pbh DbLabel: Psychology and Behavioral Sciences Collection An: 175600797 AccessLevel: 6 PubType: Academic Journal PubTypeId: academicJournal PreciseRelevancyScore: 0 |
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| Items | – Name: Title Label: Title Group: Ti Data: 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. – Name: Author Label: Authors Group: Au Data: <searchLink fieldCode="AR" term="%22Bassi%2C+Marta%22">Bassi, Marta</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Bilel%2C+Sabrine%22">Bilel, Sabrine</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Tirri%2C+Micaela%22">Tirri, Micaela</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Corli%2C+Giorgia%22">Corli, Giorgia</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Di+Rosa%2C+Fabiana%22">Di Rosa, Fabiana</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Gregori%2C+Adolfo%22">Gregori, Adolfo</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Alkilany%2C+Alaaldin+M%2E%22">Alkilany, Alaaldin M.</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Rachid%2C+Ousama%22">Rachid, Ousama</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Roda%2C+Elisa%22">Roda, Elisa</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Zauli%2C+Giorgio%22">Zauli, Giorgio</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Locatelli%2C+Carlo+Alessandro%22">Locatelli, Carlo Alessandro</searchLink> (AUTHOR)<br /><searchLink fieldCode="AR" term="%22Marti%2C+Matteo%22">Marti, Matteo</searchLink> (AUTHOR) – Name: TitleSource Label: Source Group: Src Data: <searchLink fieldCode="JN" term="%22Psychopharmacology%22">Psychopharmacology</searchLink>. Mar2024, Vol. 241 Issue 3, p489-511. 23p. – Name: Subject Label: Subjects Group: Su Data: <searchLink fieldCode="DE" term="%22Tryptamine%22">Tryptamine</searchLink><br /><searchLink fieldCode="DE" term="%22Neural+inhibition%22">Neural inhibition</searchLink><br /><searchLink fieldCode="DE" term="%22Hallucinogenic+drugs%22">Hallucinogenic drugs</searchLink><br /><searchLink fieldCode="DE" term="%22Poisoning%22">Poisoning</searchLink><br /><searchLink fieldCode="DE" term="%22Psilocybin%22">Psilocybin</searchLink><br /><searchLink fieldCode="DE" term="%22Mice%22">Mice</searchLink> – Name: Abstract Label: Abstract Group: Ab Data: 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. [ABSTRACT FROM AUTHOR] – Name: AbstractSuppliedCopyright Label: Group: Ab Data: <i>Copyright of Psychopharmacology is the property of Springer Nature and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.) |
| PLink | https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=175600797 |
| RecordInfo | BibRecord: BibEntity: Identifiers: – Type: doi Value: 10.1007/s00213-024-06526-8 Languages: – Code: eng Text: English PhysicalDescription: Pagination: PageCount: 23 StartPage: 489 Subjects: – SubjectFull: Tryptamine Type: general – SubjectFull: Neural inhibition Type: general – SubjectFull: Hallucinogenic drugs Type: general – SubjectFull: Poisoning Type: general – SubjectFull: Psilocybin Type: general – SubjectFull: Mice Type: general Titles: – TitleFull: 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. Type: main BibRelationships: HasContributorRelationships: – PersonEntity: Name: NameFull: Bassi, Marta – PersonEntity: Name: NameFull: Bilel, Sabrine – PersonEntity: Name: NameFull: Tirri, Micaela – PersonEntity: Name: NameFull: Corli, Giorgia – PersonEntity: Name: NameFull: Di Rosa, Fabiana – PersonEntity: Name: NameFull: Gregori, Adolfo – PersonEntity: Name: NameFull: Alkilany, Alaaldin M. – PersonEntity: Name: NameFull: Rachid, Ousama – PersonEntity: Name: NameFull: Roda, Elisa – PersonEntity: Name: NameFull: Zauli, Giorgio – PersonEntity: Name: NameFull: Locatelli, Carlo Alessandro – PersonEntity: Name: NameFull: Marti, Matteo IsPartOfRelationships: – BibEntity: Dates: – D: 01 M: 03 Text: Mar2024 Type: published Y: 2024 Identifiers: – Type: issn-print Value: 00333158 Numbering: – Type: volume Value: 241 – Type: issue Value: 3 Titles: – TitleFull: Psychopharmacology Type: main |
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