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• W2034308216 startingPage "331" @default.
• W2034308216 abstract "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." @default.
• W2034308216 created "2016-06-24" @default.
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• W2034308216 date "2011-05-01" @default.
• W2034308216 modified "2023-10-13" @default.
• W2034308216 title "Fentanyl–trazodone–paracetamol triple drug combination: Multimodal analgesia in a mouse model of visceral pain" @default.
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• W2034308216 doi "https://doi.org/10.1016/j.pbb.2011.01.023" @default.
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