Chair of Pharmacodynamics, Department of Pharmacodynamics, Jagiellonian University Medical College, 9 Medyczna St, 30-688, Krakow, Poland.
Faculty of Production Engineering, Warsaw University of Life Sciences, 164 Nowoursynowska St, 02-787, Warsaw, Poland.
Inflammopharmacology. 2018 Apr;26(2):361-374. doi: 10.1007/s10787-017-0405-5. Epub 2017 Oct 25.
Cebranopadol (a.k.a. GRT-6005) is a dually acting nociceptin/orphanin FQ and opioid receptor agonist that has been recently developed in Phase 2 clinical trials for painful diabetic neuropathy or cancer pain. It also showed analgesic properties in various rat models of pain and had a better safety profile as compared to equi-analgesic doses of morphine. Since antinociceptive properties of cebranopadol have been studied mainly in rat models, in the present study, we assessed analgesic activity of subcutaneous cebranopadol (10 mg/kg) in various mouse pain models.
We used models of acute, tonic, and chronic pain induced by thermal and chemical stimuli, with a particular emphasis on pharmacoresistant chronic neuropathic pain evoked by oxaliplatin in which cebranopadol was used alone or in combination with simvastatin.
As shown in the hot plate test, the analgesic activity of cebranopadol developed more slowly as compared to morphine (90-120 min vs. 60 min). Cebranopadol displayed a significant antinociceptive activity in acute pain models, i.e., the hot plate, writhing, and capsaicin tests. It attenuated nocifensive responses in both phases of the formalin test and reduced cold allodynia in oxaliplatin-induced neuropathic pain model. Its efficacy was similar to that of morphine. Used in combination and administered simultaneously, 4 or 6 h after simvastatin, cebranopadol did not potentiate antiallodynic activity of this cholesterol-lowering drug. Cebranopadol did not induce any motor deficits in the rotarod test.
Cebranopadol may have significant potential for the treatment of various pain types, including inflammatory and chemotherapy-induced neuropathic pain.
塞布兰诺啡(又名 GRT-6005)是一种双重作用的孤啡肽/孤儿受体激动剂,最近已进入 2 期临床试验,用于治疗糖尿病性神经痛或癌痛。与等效镇痛剂量的吗啡相比,它在各种疼痛大鼠模型中表现出镇痛特性,且具有更好的安全性。由于塞布兰诺啡的抗伤害感受特性主要在大鼠模型中进行了研究,因此在本研究中,我们评估了皮下注射塞布兰诺啡(10mg/kg)在各种小鼠疼痛模型中的镇痛活性。
我们使用了由热和化学刺激引起的急性、持续性和慢性疼痛模型,特别强调了奥沙利铂诱发的药物抵抗性慢性神经病理性疼痛模型,其中塞布兰诺啡单独或与辛伐他汀联合使用。
如在热板试验中所示,与吗啡(90-120min 与 60min)相比,塞布兰诺啡的镇痛活性发展较慢。塞布兰诺啡在急性疼痛模型中显示出显著的镇痛活性,即热板、扭体和辣椒素试验。它减弱了福尔马林试验的两个阶段的伤害性反应,并减轻了奥沙利铂诱导的神经病理性疼痛模型中的冷感觉过敏。其疗效与吗啡相似。联合使用,在辛伐他汀给药后 4 或 6 小时同时给予,塞布兰诺啡并未增强这种降胆固醇药物的抗感觉过敏活性。塞布兰诺啡在旋转棒试验中未引起任何运动缺陷。
塞布兰诺啡可能具有治疗各种类型疼痛的显著潜力,包括炎症和化疗引起的神经病理性疼痛。