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首页> 外文期刊>Pharmacology, Biochemistry and Behavior >Fentanyl-trazodone-paracetamol triple drug combination: multimodal analgesia in a mouse model of visceral pain.
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Fentanyl-trazodone-paracetamol triple drug combination: multimodal analgesia in a mouse model of visceral pain.

机译：芬太尼-曲唑酮-扑热息痛三联药物组合：内脏痛小鼠模型中的多峰镇痛。

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Multimodal or balanced analgesia is commonly used in the management of acute and chronic pain in humans, in order to achieve the best analgesic/safety profile. Here, by using a model of visceral acute tonic pain, the acetic acid-induced writhing test of mice, we show a synergistic interaction between fentanyl, trazodone and paracetamol on the inhibition of nociception. First of all, once assessed that all drugs induced dose-related antinociceptive effects, they were mixed in fixed ratio (1:1) combinations and a synergistic drug-drug interaction was obtained in all circumstances. Thereafter, we assayed the effects of the triple combination of fentanyl-trazodone-paracetamol and it was demonstrated that they displayed a potent synergistic interaction on the inhibition of acetic acid-mediated nociception. Interestingly, drug dosage reduction permitted to reduce the incidence of possible adverse effects, namely exploratory activity and motor coordination, thus it was demonstrated that it improved the benefit/risk profile of such treatment. Afterwards, we attempted to elucidate the mechanism of action of such interaction, by means of the non-selective opioid receptor antagonist naloxone. Interestingly, naloxone completely antagonized the antinociceptive effects of fentanyl, and it also partially reversed paracetamol and trazodone mediated analgesia. Furthermore, when naloxone was co-administered with the triple-drug treatment it blocked the previously observed enhanced antinociceptive effects of the combination. Thus, these results indicated that the endogenous opioid system played a main role in the present drug-drug interaction. Overall, the triple combination of fentanyl-trazodone-paracetamol induced a potent synergistic antinociceptive effect, which could be of interest for optimal multimodal clinical analgesia.
机译：为了获得最佳的镇痛/安全性，多峰镇痛或平衡镇痛通常用于管理人的急性和慢性疼痛。在这里，通过使用内脏急性强直性疼痛模型（乙酸诱发的小鼠扭体试验），我们显示了芬太尼，曲唑酮和扑热息痛之间在抑制伤害感受方面具有协同作用。首先，一旦评估了所有药物均诱导了剂量相关的镇痛作用，就以固定比例（1：1）的组合将它们混合，并且在所有情况下均获得了协同的药物相互作用。此后，我们测定了芬太尼-曲唑酮-扑热息痛三联组合的作用，并证明它们在抑制乙酸介导的伤害感受方面显示出强效的协同作用。有趣的是，减少药物剂量可以减少可能的不良反应（即探索活动和运动协调）的发生率，因此证明了它改善了这种治疗的获益/风险特征。之后，我们试图通过非选择性阿片受体拮抗剂纳洛酮阐明这种相互作用的作用机理。有趣的是，纳洛酮完全拮抗芬太尼的镇痛作用，并且还部分逆转了扑热息痛和曲唑酮介导的镇痛作用。此外，当将纳洛酮与三重药物治疗并用时，它阻断了先前观察到的该组合增强的抗伤害感受作用。因此，这些结果表明内源性阿片样物质系统在目前的药物-药物相互作用中起主要作用。总体而言，芬太尼-曲唑酮-扑热息痛的三联组合可产生有效的协同镇痛作用，这可能是最佳多模态临床镇痛的兴趣所在。

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