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.


Journal

Drug and alcohol dependence
ISSN: 1879-0046
Titre abrégé: Drug Alcohol Depend
Pays: Ireland
ID NLM: 7513587

Informations de publication

Date de publication:
01 11 2023
Historique:
received: 24 07 2023
revised: 24 08 2023
accepted: 28 08 2023
medline: 30 10 2023
pubmed: 18 9 2023
entrez: 17 9 2023
Statut: ppublish

Résumé

Γ-valerolactone (GVL), marketed online as "Tranquilli-G" and "excellent Valium", is used as a legal substitute for γ-hydroxybutyric acid (GHB); however, until now, GVL has only been connected to one Drug-Facilitated Sexual Assault (DFSA) case. Moreover, the pharmaco-toxicological effects of GVL are poorly studied. The aim of this study was to investigate the 1) in vivo effects of gavage administration of GVL (100-3000 mg/kg) on neurological (myoclonia, convulsions), sensorimotor (visual, acoustic, and overall tactile) responses, righting reflex, thermoregulation, motor activity (bar, drag, and accelerod test) and cardiorespiratory changes (heart rate, breath rate, oxygen saturation, and pulse distension) in CD-1 male mice and the 2) in silico ADMET profile of GVL in comparison to GHB and the open active form γ-hydroxyvaleric acid (GHV). The present study demonstrates that GVL inhibits, in a dose-dependent manner, sensorimotor and motor responses and induces cardiorespiratory depression (at a dose of 3000 mg/kg) in mice. The determination of the ED

Identifiants

pubmed: 37717308
pii: S0376-8716(23)01189-4
doi: 10.1016/j.drugalcdep.2023.110951
pii:
doi:

Substances chimiques

4-hydroxybutyric acid 30IW36W5B2
gamma-valerolactone O7056XK37X
Sodium Oxybate 7G33012534
Hydroxybutyrates 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

110951

Informations de copyright

Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of Competing Interest Declarations of interest: none.

Auteurs

Raffaella Arfè (R)

Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy.

Sabrine Bilel (S)

Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy.

Micaela Tirri (M)

Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy.

Giorgia Corli (G)

Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy.

Eva Bergamin (E)

Università Cattolica del Sacro Cuore, Roma, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy.

Giovanni Serpelloni (G)

Neuroscience Clinical Center & TMS Unit, VR, Italy.

Marta Bassi (M)

Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy.

Martina Borsari (M)

Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy.

Federica Boccuto (F)

Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy.

Tatiana Bernardi (T)

Department of Environmental Sciences and Prevention University of Ferrara, Ferrara, Italy.

Lorenzo Caruso (L)

Department of Environmental Sciences and Prevention University of Ferrara, Ferrara, Italy.

Alaaldin M Alkilany (AM)

Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Qatar.

Ousama Rachid (O)

Department of Pharmaceutical Sciences, College of Pharmacy, QU Health, Qatar University, Qatar.

Francesco Botrè (F)

Antidoping Laboratory FMSI, Rome, Italy; REDs - Research and Expertise in antidoping Sciences, ISSUL - Institute of Sport Sciences, University of Lausanne, Lausanne, Switzerland.

Fabio De-Giorgio (F)

Università Cattolica del Sacro Cuore, Roma, Italy; Fondazione Policlinico Universitario A. Gemelli IRCCS, Roma, Italy. Electronic address: fabio.degiorgio@unicatt.it.

Matteo Marti (M)

Department of Translational Medicine, Section of Legal Medicine and LTTA Centre, University of Ferrara, Ferrara, Italy; Collaborative Center for the Italian National Early Warning System, Department of Anti-Drug Policies, Presidency of the Council of Ministers, Italy. Electronic address: matteo.marti@unife.it.

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Classifications MeSH