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褪黑素与 N-棕榈酰乙醇酰胺和对乙酰氨基酚的镇痛作用协同增效。

Melatonin synergizes with the antinociceptive effect of N-palmitoylethanolamide and paracetamol.

机构信息

Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Ciudad de México.

Facultad de Ciencias Químico-Biológicas, Universidad Autónoma de Sinaloa, Culiacán, Sinaloa.

出版信息

Pharmazie. 2022 Sep 1;77(7):236-242. doi: 10.1691/ph.2022.2428.

DOI:10.1691/ph.2022.2428
PMID:36199181
Abstract

Melatonin has been shown to have an antinociceptive effect and its administration could enhance the antinociceptive effect of other drugs. This study assessed the antinociceptive effects of melatonin in combination with paracetamol and N-palmitoylethanolamide (PEA) using the formalin test in mice. Melatonin, paracetamol, and PEA were administered intraplantarly (paw) alone or combined to mice. A concentration-response curve was generated to determine the concentration needed to reach 30% of the maximal antinociceptive effect (EC). Melatonin, paracetamol and PEA induced a concentration-dependent antinociceptive effect in both phases of the formalin test, being PEA more potent (EC = 7.4±0.2 mg/paw) than melatonin (EC = 20.5±3.1 mg/paw) or paracetamol (EC = 41.8±2.6 mg/paw). Combinations of melatonin with paracetamol or PEA also induced a concentration-dependent antinociceptive effect in the formalin test. Isobolographic analysis showed that melatonin interacts synergistically with either paracetamol or PEA to reduce formalin-induced inflammatory pain. However, the experimental values of EC were significantly smaller than those calculated theoretically.

摘要

褪黑素具有镇痛作用,其给药可以增强其他药物的镇痛作用。本研究使用小鼠福尔马林试验评估了褪黑素与扑热息痛和 N-棕榈酰乙醇酰胺 (PEA) 联合使用的镇痛作用。褪黑素、扑热息痛和 PEA 单独或联合给药于足底。生成浓度-反应曲线以确定达到最大镇痛作用 30%所需的浓度(EC)。褪黑素、扑热息痛和 PEA 在福尔马林试验的两个阶段均引起浓度依赖性镇痛作用,PEA 的效力(EC = 7.4±0.2 mg/足)强于褪黑素(EC = 20.5±3.1 mg/足)或扑热息痛(EC = 41.8±2.6 mg/足)。褪黑素与扑热息痛或 PEA 的组合也在福尔马林试验中引起浓度依赖性镇痛作用。等辐射分析表明,褪黑素与扑热息痛或 PEA 相互作用协同,以减轻福尔马林诱导的炎症性疼痛。然而,EC 的实验值明显小于理论上计算的值。

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