Synergistic interaction between diclofenac and pyrilamine on nociception, inflammation, and gastric damage in rats

Experiments using nonsteroidal anti-inflammatory drugs (NSAIDs) alone have produced limited antinociceptive effects in animal models. For this reason, the number of studies involving the administration of NSAIDs along with an adjuvant drug harboring different mechanisms of action has increased enormously. Here, combinations of diclofenac and pyrilamine were used to determine their influence on nociception (formalin test), inflammation (paw inflammation produced by carrageenan), and gastric damage in rodents. Diclofenac, pyrilamine, or combinations of diclofenac and pyrilamine produced antinociceptive and anti-inflammatory effects in the rat. The systemic administration of diclofenac alone and in combination with pyrilamine produced significant gastric damage. Effective dose (ED) values were determined for each individual drug, and isobolograms were prepared. The theoretical ED values for the antinociceptive (systemic, 35.4 mg/kg; local, 343.4 μg/paw) and the anti-inflammatory (37.9 mg/kg) effects differed significantly from the experimental ED values (systemic antinociception, 18.1 mg/kg; local antinociception, 183.3 μg/paw; anti-inflammation, 10.6 mg/kg). Therefore, it was concluded that the interactions between diclofenac and pyrilamine are synergistic. The data suggest that the diclofenac-pyrilamine combinations can interact at the systemic and local peripheral levels, thereby offering a therapeutic alternative for the clinical management of inflammatory pain.