GW 405833 (L-768242) is an agonist of cannabinoid-2 (CB(2)) receptor-selective

GW405833 (3、10及30 mg/kg i.p.) 在WT小鼠的两种疼痛模型中剂量依赖性地逆转了已建立的机械性痛觉过敏；然而，GW405833的抗痛觉过敏效果在CB2KO小鼠中完全保留，而在CB1KO小鼠中则完全缺失。此外，GW405833（30 mg/kg i.p.）的抗痛觉过敏效能被CB1拮抗剂rimonabant（10 mg/kg i.p.）完全阻断，但不被CB2拮抗剂SR144528（10 mg/kg i.p.）阻断。因此，GW405833的抗痛效果依赖于CB1受体。在测量CB1激活的四项主要征象的测试中，GW405833（30 mg/kg i.p.）也显示无活性。此外，与rimonabant（10 mg/kg i.p.）不同，GW405833（10 mg/kg, i.p.）在体内不作为CB1拮抗剂，不会在经Δ9-tetrahydrocannabinol长期处理的小鼠中引发撤回症状。

Baseline mechanical paw withdrawal thresholds were measured in each paw for each animal before performing either PSNL or injecting CFA.?Another predrug baseline was then taken after painful peripheral neuropathy or inflammatory pain was fully established.?GW405833 was administered (i.p.) 30 minutes before evaluation of the impact of drug manipulations on mechanical paw withdrawal thresholds.?Different doses of GW405833 were injected (i.p.) within subjects in the order of vehicle (0), 3, 10, and 30 mg/kg.?Sufficient time was allowed to lapse between each dose to verify that mechanical paw withdrawal thresholds returned to the predrug levels before dose escalation. .?In the groups where CB1 or CB2 antagonists were tested, rimonabant or SR144528 (10 mg/kg i.p.) was administered 20 minutes before GW405833 injection[1].