Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat
Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat
复制标题
DOI：
10.1038/sj.bjp.0704466
复制
发表时间：
2002-01-01
影响因子：
7.3
通讯作者：
Giagnoni, G
中科院分区：
文献类型：
--
作者：
Conti, S;Costa, B;Giagnoni, G
1 在角叉菜胶诱导的急性后爪炎症大鼠模型中，合成大麻素大麻隆的抗炎活性与内源性大麻素棕榈酰乙醇酰胺和非甾体抗炎药吲哚美辛的抗炎活性进行了比较。2 大鼠的初步实验使用了四组行为测试，专门针对中枢神经系统中的四氢大麻酚型活性。这些结果表明，口服剂量的大麻隆 2.5 mg kg(-1) 没有大麻素精神活性。3 足底注射角叉菜胶 (1% w v(-1)) 会引起爪子体积和热痛觉过敏的时间依赖性增加。4 在角叉菜胶前 1 小时给予大麻隆（0.75、1.5、2.5 mg kg(-1)，口服），可减少水肿和相关的痛觉过敏以剂量相关的方式出现。大麻隆 2.5 mg kg(-1)、棕榈酰乙醇酰胺 10 mg kg(-1) 和吲哚美辛 5 mg kg(-1)，口服给药。卡拉胶前 1 小时，也以时间依赖性方式降低炎症参数。5 选择性 CB2 大麻素受体拮抗剂 {N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1]heptan-2-yl]-5-(4-氯-3-甲基苯基)-1-(4-甲基苄基)吡唑-3 甲酰胺} (SR 144528), 3毫克 千克(-1) 口服在大麻酮和棕榈酰乙醇酰胺之前 1 小时，在角叉菜胶之后 3 小时，阻止了两种大麻素激动剂的抗水肿和抗痛觉过敏作用。6 我们的研究结果显示了大麻酮的抗炎作用，并证实了棕榈酰乙醇酰胺的抗炎作用，表明这些作用是由一种未表征的 CB2 样大麻素受体介导的。
1 The antiinflammatory activity of synthetic cannabinoid nabilone in the rat model of carrageenan-induced acute hindpaw inflammation was compared with that of the endocannabinoid palmitoylethanolamide and the nonsteroidal antiinflammatory drug indomethacin.2 Preliminary experiments in rats used a tetrad of behavioural tests, specific for tetrahydrocannabinol-type activity in the CNS. These showed that the oral dose of nabilone 2.5 mg kg(-1) had no cannabinoid psychoactivity.3 Intraplantar injection of carrageenan (1% w v(-1)) elicited a time-dependent increase in paw volume and thermal hyperalgesia.4 Nabilone (0.75, 1.5, 2.5 mg kg(-1), p.o.), given 1 h before carrageenan, reduced the development of oedema and the associated hyperalgesia in a dose-related manner. Nabilone 2.5 mg kg(-1), palmitoylethanolamide 10 mg kg(-1) and indomethacin 5 mg kg(-1), given p.o. 1 h before carrageenan, also reduced the inflammatory parameters in a time-dependent manner.5 The selective CB2 cannabinoid receptor antagonist {N-[(1S)-endo-1,3,3-trimethyl bicyclo [2.2.1]heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)pyrazole-3 carboxamide} (SR 144528), 3 mg kg(-1) p.o. 1 h before nabilone and palmitoylethanolamide, prevented the anti-oedema and antihyperalgesic effects of the two cannabinoid agonists 3 h after carrageenan.6 Our findings show the antiinflammatory effect of nabilone and confirm that of palmitoylethanolamide indicating that these actions are mediated by an uncharacterized CB2-like cannabinoid receptor.