The objective of this study was to investigate spinal and supraspinal antinociceptive effects of a new synthetic compound, (+/-)-cis-(6-ethyl-tetrahydropyran-2-yl)-formic acid (tetrahydropyran derivative). Its activity was compared with those from morphine. In peripheral models of inflammation and hyperalgesia, tetrahydropyran derivative significantly reduced nociceptive effect induced by acetic acid or formalin in mice. Tetrahydropyran derivative developed antinociceptive effect on the tail-flick and hot-plate tests with a long-acting curve maintaining the effect for 4 h longer than morphine. The opioid receptor antagonist naloxone totally reverted tetrahydropyran derivative effects on both models. Morphine as well as tetrahydropyran derivative induced tolerance and sedation in mice. However, tetrahydropyran derivative-induced tolerance had its onset retarded and the sedative activity was lower when compared to that induced by morphine. These results indicate that this new substance develops an antinociceptive activity and may be used in the future as a substitute for traditional opioids.

译文

这项研究的目的是研究一种新的合成化合物 (/-)-顺式-(6-乙基-四氢吡喃-2-基)-甲酸 (四氢吡喃衍生物) 的脊柱和脊髓上镇痛作用。将其活性与吗啡的活性进行了比较。在炎症和痛觉过敏的外周模型中,四氢吡喃衍生物显着降低了乙酸或福尔马林对小鼠的伤害感受作用。四氢吡喃衍生物对甩尾和热板试验产生了抗伤害感受作用,其长效曲线比吗啡保持作用4小时。阿片受体拮抗剂纳洛酮在两种模型上都完全恢复了四氢吡喃衍生物的作用。吗啡以及四氢吡喃衍生物可诱导小鼠耐受和镇静。然而,与吗啡相比,四氢吡喃衍生物诱导的耐受性的发作延迟,镇静活性较低。这些结果表明,这种新物质具有抗伤害感受活性,将来可能用作传统阿片类药物的替代品。

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