A major glucuronidated metabolite of JWH-018 is a neutral antagonist at CB1 receptors.
A major glucuronidated metabolite of JWH-018 is a neutral antagonist at CB1 receptors.
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JWH-018 的主要葡萄糖醛酸化代谢物是 CB1 受体的中性拮抗剂。
DOI：
10.1021/tx3000472
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发表时间：
2012
影响因子：
4.1
通讯作者：
Prather,PaulL
中科院分区：
文献类型：
--
作者：
Seely,KathrynA;Brents,LisaK;Radominska-Pandya,Anna;Endres,GregoryW;Keyes,GregoryS;Moran,JefferyH;Prather,PaulL
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) β-d-glucuronide (018-gluc), for CB1Rs. The 018-gluc binds CB1Rs (Ki= 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.
