The monoacylglycerol lipase inhibitor JZL184 suppresses inflammatory pain in the mouse carrageenan model.
The monoacylglycerol lipase inhibitor JZL184 suppresses inflammatory pain in the mouse carrageenan model.
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单酰基甘油脂肪酶抑制剂JZL184抑制小鼠角叉菜胶模型中的炎症疼痛。
DOI：
10.1016/j.lfs.2012.06.020
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发表时间：
2013-03-19
期刊：
影响因子：
6.1
通讯作者：
Lichtman, Aron H.
中科院分区：
文献类型：
--
作者：
Ghosh, Sudeshna;Wise, Laura E.;Chen, Yugang;Gujjar, Ramesh;Mahadevan, Anu;Cravatt, Benjamin F.;Lichtman, Aron H.
关键词：
本研究测试了选择性单酰基甘油脂肪酶（MAGL）抑制剂JZL 184是否会减少角叉菜胶试验中的异常性疼痛和爪水肿。将JZL 184的抗水肿和抗异常性疼痛作用与PF-3845（脂肪酸酰胺水解酶（FAAH）抑制剂）和双氯芬酸（非选择性环氧合酶抑制剂）进行比较。通过给予相应的CB 1和CB 2受体拮抗剂利莫那班和SR 144528以及CB 1（−/−）和CB 2（−/−）小鼠，评价大麻素受体参与JZL 184的抗水肿和抗异常性疼痛作用。施用JZL 184（1.6、4、16或40 mg/kg）六天以评估耐受性。在角叉菜胶之前或之后给予JZL 184显著减轻角叉菜胶诱导的爪水肿和机械性异常性疼痛。互补的遗传学和药理学方法表明，JZL 184的抗异常性疼痛作用需要CB 1和CB 2受体，但只有CB 2受体介导其抗水肿作用。重要的是，在重复注射高剂量JZL 184（16或40 mg/kg）后，抗水肿和抗异常性疼痛作用均经历耐受，但重复施用低剂量JZL 184（4 mg/kg）保留功效。这些结果表明，MAGL抑制剂JZL 184通过激活CB 1和CB 2受体减少炎症性伤害感受，在重复施用低剂量后没有耐受性的证据。
The present study tested whether the selective monoacylglycerol lipase (MAGL) inhibitor JZL184 would reduce allodynia and paw edema in the carrageenan test. The anti-edematous and anti-allodynic effects of JZL184 were compared to those of PF-3845, an inhibitor of fatty acid amide hydrolase (FAAH), and diclofenac, a non-selective cyclooxygenase inhibitor. Cannabinoid receptor involvement in the anti-edematous and anti-allodynic effects of JZL184 was evaluated by administration of the respective CB1 and CB2 receptor antagonists rimonabant and SR144528 as well as with CB1(−/−) and CB2(−/−) mice. JZL184 (1.6, 4, 16, or 40 mg/kg) was administered for six days to assess tolerance. JZL184 administered before or after carrageenan significantly attenuated carrageenan-induced paw edema and mechanical allodynia. Complementary genetic and pharmacological approaches revealed that the anti-allodynic effects of JZL184 required both CB1 and CB2 receptors, but only CB2 receptors mediated its anti-edematous actions. Importantly, both the anti-edematous and anti-allodynic effects underwent tolerance following repeated injections of high dose JZL184 (16 or 40 mg/kg), but repeated administration of low dose JZL184 (4 mg/kg) retained efficacy. These results suggest that the MAGL inhibitor JZL184 reduces inflammatory nociception through the activation of both CB1 and CB2 receptors, with no evidence of tolerance following repeated administration of low doses.
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影响因子：
3.6
作者：
Dinh, TP;Kathuria, S;Piomelli, D
通讯作者：
Piomelli, D
人体免疫组织和白细胞亚群中枢和外周大麻素受体的表达
DOI：
10.1111/j.1432-1033.1995.tb20780.x
发表时间：
1995-08-15
期刊：
EUROPEAN JOURNAL OF BIOCHEMISTRY
影响因子：
--
作者：
GALIEGUE, S;MARY, S;CASELLAS, P
通讯作者：
CASELLAS, P
影响因子：
7.3
作者：
Conti, S;Costa, B;Giagnoni, G
通讯作者：
Giagnoni, G
影响因子：
7.3
作者：
Comelli, F.;Giagnoni, G.;Costa, B.
通讯作者：
Costa, B.
影响因子：
5
作者：
Gallily, R;Breuer, A;Mechoulam, R
通讯作者：
Mechoulam, R