Fiche du document
21 juillet 2022
- doi: 10.3390/ijms23148030
- issn: 1422-0067
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/doi/10.3390/ijms23148030
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/pmid/35887377
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/eissn/1422-0067
Ce document est lié à :
info:eu-repo/semantics/altIdentifier/urn/urn:nbn:ch:serval-BIB_BB8B93BEDC233
info:eu-repo/semantics/openAccess , CC BY 4.0 , https://creativecommons.org/licenses/by/4.0/
Sujets proches
Mouse House mice Mus musculus House mouseCiter ce document
M. Tirri et al., « In Vivo Bio-Activation of JWH-175 to JWH-018: Pharmacodynamic and Pharmacokinetic Studies in Mice. », Serveur académique Lausannois, ID : 10.3390/ijms23148030
Métriques
Partage / Export
Résumé
3-(1-Naphthalenylmethyl)-1-pentyl-1H-indole (JWH-175) is a synthetic cannabinoid illegally marketed for its psychoactive cannabis-like effects. This study aimed to investigate and compare in vitro and in vivo pharmacodynamic activity of JWH-175 with that of 1-naphthalenyl (1-pentyl-1H-indol-3-yl)-methanone (JWH-018), as well as evaluate the in vitro (human liver microsomes) and in vivo (urine and plasma of CD-1 male mice) metabolic profile of JWH-175. In vitro binding studies showed that JWH-175 is a cannabinoid receptor agonist less potent than JWH-018 on mouse and human CB1 and CB2 receptors. In agreement with in vitro data, JWH-175 reduced the fESPS in brain hippocampal slices of mice less effectively than JWH-018. Similarly, in vivo behavioral studies showed that JWH-175 impaired sensorimotor responses, reduced breath rate and motor activity, and increased pain threshold to mechanical stimuli less potently than JWH-018. Metabolic studies demonstrated that JWH-175 is rapidly bioactivated to JWH-018 in mice blood, suggesting that in vivo effects of JWH-175 are also due to JWH-018 formation. The pharmaco-toxicological profile of JWH-175 was characterized for the first time, proving its in vivo bio-activation to the more potent agonist JWH-018. Thus, it highlighted the great importance of investigating the in vivo metabolism of synthetic cannabinoids for both clinical toxicology and forensic purposes.