Fentanyl–trazodone–paracetamol triple drug combination: Multimodal analgesia in a mouse model of visceral pain
| Autor: | Raquel Poveda, Alejandro Fernández, Víctor Fernández-Dueñas, Francisco Ciruela, Silvia Sánchez, Eulalia Planas |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.drug_class Clinical Biochemistry Analgesic Pain Pharmacology Toxicology Biochemistry Fentanyl Mice Behavioral Neuroscience Opioid receptor medicine Animals Biological Psychiatry Acetaminophen Endogenous opioid Analgesics business.industry Chronic pain Trazodone Visceral pain medicine.disease Disease Models Animal Drug Combinations Nociception Rotarod Performance Test medicine.symptom business medicine.drug |
| Zdroj: | Pharmacology Biochemistry and Behavior. 98:331-336 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/j.pbb.2011.01.023 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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