Titre
In Vivo Bio-Activation of JWH-175 to JWH-018: Pharmacodynamic and Pharmacokinetic Studies in Mice.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Tirri, M.
Auteure/Auteur
Arfè, R.
Auteure/Auteur
Bilel, S.
Auteure/Auteur
Corli, G.
Auteure/Auteur
Marchetti, B.
Auteure/Auteur
Fantinati, A.
Auteure/Auteur
Vincenzi, F.
Auteure/Auteur
De-Giorgio, F.
Auteure/Auteur
Camuto, C.
Auteure/Auteur
Mazzarino, M.
Auteure/Auteur
Barbieri, M.
Auteure/Auteur
Gaudio, R.M.
Auteure/Auteur
Varani, K.
Auteure/Auteur
Borea, P.A.
Auteure/Auteur
Botrè, F.
Auteure/Auteur
Marti, M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1422-0067
Statut éditorial
Publié
Date de publication
2022-07-21
Volume
23
Numéro
14
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
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.
PID Serval
serval:BIB_BB8B93BEDC23
PMID
Open Access
Oui
Date de création
2023-04-03T10:03:56.525Z
Date de création dans IRIS
2025-05-20T21:42:25Z
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Nom
ijms-23-08030.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
3.37 MB
Format
Adobe PDF
PID Serval
serval:BIB_BB8B93BEDC23.P001
URN
urn:nbn:ch:serval-BIB_BB8B93BEDC233
Somme de contrôle
(MD5):9e2addb35f5b3e61b7ee0896ac2feb86