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

Publication: Drug Alcohol Dep
Keywords: GB, GHB, GHV, GVL
Software: ADMET Predictor®
Therapeutic Areas: CNS


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 reflexthermoregulation, 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 ED50 in sensorimotor and motor responses revealed that GVL is about 4–5 times less potent than GHB. In silico prediction of ADMET profiles revealed toxicokinetic similarities between GHB and GHV, and differences with GVL. These results suggest that GVL could be used as a substitute for GHB and should be added to forensic toxicology screenings.

By Raffaella Arfè, Sabrine Bilel, Micaela Tirri, Giorgia Corli, Eva Bergamin, Giovanni Serpelloni, Marta Bassi, Martina Borsari, Federica Boccuto, Tatiana Bernardi, Lorenzo Caruso, Alaaldin. Alkilany, Ousama Rachid, Francesco Botrè, Fabio De-Giorgio, Matteo Marti