Miranda Hugo F, Puig Margarita M, Dursteler Christian, Prieto Juan Carlos, Pinardi Gianni
Pharmacology Program, ICBM, Faculty of Medicine, University of Chile, Clasificador 70.000, Independencia 1027, Santiago 7, Chile.
Neuropharmacology. 2007 Feb;52(2):291-6. doi: 10.1016/j.neuropharm.2006.07.025. Epub 2006 Oct 30.
The antinociceptive activity of dexketoprofen was studied in mice using the acetic acid writhing test (acute tonic pain), the tail flick test (acute phasic pain) and the formalin assay (inflammatory pain). Isobolographic analysis was used to study the antinociceptive interactions between morphine and paracetamol co-administered with dexketoprofen. In the writhing test, the intraperitoneal administration of dexketoprofen or ketoprofen resulted in parallel dose-response curves with equal efficacy, but higher relative potency for dexketoprofen. In the tail flick test, the curves were parallel with similar efficacy and potency. The administration of morphine or paracetamol in both tests resulted in dose-response curves not parallel with that of dexketoprofen, which showed a potency between morphine and paracetamol. In the formalin assay, the antinociceptive activity of morphine during phase I was 122, 295 and 1695 times higher than dexketoprofen, ketoprofen and paracetamol, respectively. Isobolographic analysis demonstrated that the combination of sub-analgesic doses of dexketoprofen with morphine or with paracetamol was strongly synergic in all three tests. Synergistic drug combinations should improve effective pharmacological treatment of pain, minimizing drug specific adverse effects. These findings are undoubtedly worthy of additional controlled clinical trials in severe pain syndromes.
使用醋酸扭体试验（急性持续性疼痛）、甩尾试验（急性阵发性疼痛）和福尔马林试验（炎性疼痛）在小鼠中研究了右酮洛芬的抗伤害感受活性。采用等效应线分析来研究吗啡和对乙酰氨基酚与右酮洛芬联合给药时的抗伤害感受相互作用。在扭体试验中，腹腔注射右酮洛芬或酮洛芬产生了具有同等效力的平行剂量 - 反应曲线，但右酮洛芬的相对效价更高。在甩尾试验中，曲线平行，效力和效能相似。在这两个试验中，吗啡或对乙酰氨基酚的给药产生的剂量 - 反应曲线与右酮洛芬的不平行，右酮洛芬的效价介于吗啡和对乙酰氨基酚之间。在福尔马林试验中，吗啡在第一阶段的抗伤害感受活性分别比右酮洛芬、酮洛芬和对乙酰氨基酚高122倍、295倍和1695倍。等效应线分析表明，在所有三个试验中，亚镇痛剂量的右酮洛芬与吗啡或与对乙酰氨基酚联合使用均具有强协同作用。协同药物组合应能改善疼痛的有效药物治疗，将药物特异性不良反应降至最低。这些发现无疑值得在严重疼痛综合征中进行更多的对照临床试验。
