Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Mexico.
Departamento de Sistemas Biológicos, Universidad Autónoma Metropolitana, Unidad Xochimilco, Ciudad de México, Mexico.
Drug Dev Res. 2018 Dec;79(8):400-405. doi: 10.1002/ddr.21476. Epub 2018 Oct 26.
Preclinical Research & Development The purpose of this study was to assess the interaction and mechanisms of action of the paracetamol-tapentadol combination in the formalin-induced pain model in mice. Paracetamol (56.23-562.3 mg/kg, i.p.) or tapentadol (1-10 mg/kg, i.p.) were administered 15 min prior the intraplantar injection of formalin. The ED value of each drug was determined through the dose-response curves. The ED values were used to calculate the combinations in three fixed proportions (1:1, 1:3, and 3:1). Naloxone (1 and 5 mg/kg, i.p.), L-NAME (3 mg/kg, i.p.), or glibenclamide (10 mg/kg, i.p.) were administered before the combination of drugs to evaluate the antinociceptive mechanisms of action. The results showed that the combination 1:1 and paracetamol3-tapenadol1 ratios produced additive effects, whereas the paracetamol1-tapentadol3 proportion showed an antinociceptive synergistic interaction. Moreover, naloxone and glibenclamide reversed the antinociceptive activity of the paracetamol-tapentadol mixture. Our results indicate that the paracetamol-tapentadol combination produces an antinociceptive synergistic interaction with the possible participation of ATP-sensitive K+ channels and μ-opioid receptors in the second phase of the formalin-induced pain model in mice.
临床前研究与开发
本研究旨在评估对乙酰氨基酚-曲马多联合在小鼠福尔马林诱导疼痛模型中的相互作用和作用机制。对乙酰氨基酚（56.23-562.3mg/kg，腹腔注射）或曲马多（1-10mg/kg，腹腔注射）于福尔马林皮下注射前 15 分钟给药。通过剂量-反应曲线确定每种药物的 ED 值。使用 ED 值计算三种固定比例（1:1、1:3 和 3:1）的组合。纳洛酮（1 和 5mg/kg，腹腔注射）、L-NAME（3mg/kg，腹腔注射）或格列本脲（10mg/kg，腹腔注射）在给药前给予药物组合，以评估其镇痛作用机制。结果表明，1:1 和 3:1 的比例产生相加作用，而 1:3 的比例表现出协同镇痛作用。此外，纳洛酮和格列本脲逆转了对乙酰氨基酚-曲马多混合物的镇痛作用。我们的结果表明，对乙酰氨基酚-曲马多联合在小鼠福尔马林诱导疼痛模型的第二阶段产生协同镇痛作用，可能涉及 ATP 敏感性钾通道和μ阿片受体。
