Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide
Antinociceptive activity of the endogenous fatty acid amide, palmitylethanolamide
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DOI：
10.1016/s0014-2999(01)00988-8
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发表时间：
2001-05-11
影响因子：
5
通讯作者：
Piomelli, D
中科院分区：
文献类型：
--
作者：
Calignano, A;La Rana, G;Piomelli, D
内源性脂肪酸乙醇酰胺、棕榈乙醇酰胺减少。以剂量依赖性方式，通过注射福尔马林（5%，足底内）、乙酸（0.6%，每只动物0.5ml，腹膜内，i. p.）高岭土（每只动物2.5mg，i. p.），和硫酸镁（120 mg/kg，i. p.）。棕榈乙醇酰胺的抗伤害作用被大麻素CB 2受体拮抗剂SR 144528 [N-（[1 s]-内-1.3.3-三甲基双环[2.3.1][4-甲基苄基）-吡唑-3-甲酰胺]不受大麻素CB，受体拮抗剂SR 141716 A [N-（哌啶-1-基）-5-（4-氯苯基）-1-（2，4-二氯苯基）-4-甲基-1H-吡唑-3-甲酰胺.HCl]。相比之下，棕榈乙醇胺对辣椒素诱发的疼痛行为或热伤害性感受没有影响。内源性大麻素，花生四烯酸乙醇酰胺（arachidonethanolamide），减轻所有测试（福尔马林，乙酸，高岭土，硫酸镁，辣椒素和热板）的伤害感受。这些作用被大麻素CB 1受体拮抗剂SR 141716 A阻止，而不是大麻素CB 1受体拮抗剂SR 141716 A。额外的脂肪酸乙醇酰胺（油基乙醇酰胺，肉豆蔻基乙醇酰胺，棕榈油基乙醇酰胺，棕榈酰乙醇酰胺）对福尔马林诱发的疼痛行为几乎没有影响或没有影响，并且没有在其他疼痛模型中进行研究。这些结果支持了内源性棕榈乙醇酰胺参与疼痛起始的内在控制的假设。他们还表明，棕榈乙醇酰胺激活的假定受体位点可能为外周作用镇痛药物提供一个新的靶点。(C)2001 Elsevier Science B. V.保留所有权利。
The endogenous fatty acid ethanolamide, palmitylethanolamide, alleviated. in a dose-dependent manner, pain behaviors elicited in mice by injections of formalin (5%, intraplantar), acetic acid (0.6%, 0.5 mi per animal, intraperitoneal, i.p.), kaolin (2.5 mg per animal, i.p.), and magnesium sulfate (120 mg per kg, i.p.). The antinociceptive effects of palmitylethanolamide were prevented by the cannabinoid CB2 receptor antagonist SR144528 [N-([1 s]-endo-1.3.3-trimethylbicyclo[2.3.1]he (4-methylbenzyl)-pyrazole-3-carboxamide] not by the cannabinoid CB, receptor antagonist SR141716A [N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide.HCl]. By contrast, palmitylethanolamide had no effect on capsaicin-evoked pain behavior or thermal nociception. The endogenous cannabinoid, anandamide (arachidonylethanolamide), alleviated nociception in all tests (formalin, acetic acid, kaolin, magnesium sulfate, capsaicin and hot plate). These effects were prevented by the cannabinoid CB1 receptor antagonist SR141716A, not the cannabinoid CB1 receptor antagonist SR141716A. Additional fatty acid ethanolamides (oleylethanolamide, myristylethanolamide, palmitoleylethanolamide, palmitelaidylethanolamide) had little or no effect on formalin-evoked pain behavior, and were not investigated in other pain models. These results support the hypothesis that endogenous palmitylethanolamide participates in the intrinsic control of pain initiation. They also suggest that the putative receptor site activated by palmitylethanolamide may provide a novel target for peripherally acting analgesic drugs. (C) 2001 Elsevier Science B.V. All rights reserved.