School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, PR China.
School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, 264005, PR China; State Key Laboratory of Long-acting and Targeting Drug Delivery Technologies, Luye Pharma Group Ltd., Yantai, Shandong, 264003, PR China.
Eur J Pharmacol. 2021 Jan 15;891:173693. doi: 10.1016/j.ejphar.2020.173693. Epub 2020 Nov 6.
Rotigotine-loaded microspheres (RoMS) are sustained-release formulations with prolonged anti-Parkinson's effects. Given that pain is a non-motor symptom of Parkinson's disease, this study investigated the antinociceptive effects of RoMS and their synergistic effects with analgesics on inflammatory pain. A model of inflammatory pain was prepared by intraplantarly injecting male Sprague-Dawley rats with carrageenan. The antinociceptive effects of RoMS, acetaminophen, and tramadol, both alone and in combination, were evaluated using the hind paw withdrawal latency in the hot plate test and Randall-Selitto test. The rotigotine concentrations in serum and tissues were assayed using ultra-performance liquid chromatography-tandem mass spectrometry. Isobolographic analysis was performed to evaluate the nature of the interactions of RoMS with acetaminophen or tramadol. The results showed that hind paw withdrawal latency to thermal and mechanical stimuli was significantly increased on day 3 and 7 after administered RoMS. Rotigotine could be detected in serum and tissues 3 and 7 days after an intramuscular injection of RoMS. However, the rotigotine concentration fell the detection limit of the assay on day 14 after administration. RoMS produced synergistic antinociceptive effects in the inflammatory pain model when RoMS is combined with acetaminophen or tramadol. These findings suggest that RoMS can relieve inflammatory pain in rats. Furthermore, the combination of RoMS with acetaminophen or tramadol produces synergistic antinociception, which may be clinically worthy because combination therapies may reduce the drug doses required for antinociception.
罗替高汀微球（RoMS）是一种具有延长抗帕金森作用的缓释制剂。鉴于疼痛是帕金森病的一种非运动症状，本研究探讨了 RoMS 的镇痛作用及其与镇痛药对炎性疼痛的协同作用。通过向雄性 Sprague-Dawley 大鼠足底注射角叉菜胶制备炎性疼痛模型。使用热板试验和 Randall-Selitto 试验评估 RoMS、对乙酰氨基酚和曲马多单独和联合使用时的抗伤害作用。使用超高效液相色谱-串联质谱法测定血清和组织中的罗替高汀浓度。采用等对数分析评价 RoMS 与对乙酰氨基酚或曲马多相互作用的性质。结果表明，RoMS 给药后第 3 天和第 7 天，热和机械刺激的后爪退缩潜伏期显著延长。RoMS 肌肉注射后 3 天和 7 天可在血清和组织中检测到罗替高汀。然而，给药后第 14 天，罗替高汀浓度降至检测限以下。RoMS 与对乙酰氨基酚或曲马多联合使用时，在炎性疼痛模型中产生协同镇痛作用。这些发现表明，RoMS 可减轻大鼠的炎性疼痛。此外，RoMS 与对乙酰氨基酚或曲马多联合使用可产生协同镇痛作用，这在临床上可能具有价值，因为联合治疗可能减少镇痛所需的药物剂量。
