A major glucuronidated metabolite of JWH-018 is a neutral antagonist at CB1 receptors.
Chem Res Toxicol
; 25(4): 825-7, 2012 Apr 16.
Article
in En
| MEDLINE
| ID: mdl-22404317
ABSTRACT
Recently, hydroxylated metabolites of JWH-018, a synthetic cannabinoid found in many K2/Spice preparations, have been shown to retain affinity and activity for cannabinoid type 1 receptors (CB1Rs). The activity of glucuronidated metabolites of JWH-018 is not known; hence, this study investigated the affinity and activity of a major metabolite, JWH-018-N-(5-hydroxypentyl) ß-D-glucuronide (018-gluc), for CB1Rs. The 018-gluc binds CB1Rs (K(i) = 922 nM), has no effect on G-protein activity, but antagonizes JWH-018 activity at CB1Rs. The data suggests that hydroxylation by cytochrome P450s and subsequent glucuronidation by UDP-glucuronosyltransferases produces a metabolite, 018-gluc, which possesses antagonistic activity at CB1Rs.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptor, Cannabinoid, CB1
/
Indoles
/
Naphthalenes
Limits:
Humans
Language:
En
Journal:
Chem Res Toxicol
Journal subject:
TOXICOLOGIA
Year:
2012
Document type:
Article
Affiliation country: