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      Pharmacological profile of parecoxib: a novel, potent injectable selective cyclooxygenase-2 inhibitor.

      European Journal of Pharmacology
      Acetic Acid, Animals, Carrageenan, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Cyclooxygenase Inhibitors, pharmacology, Dose-Response Relationship, Drug, Edema, chemically induced, prevention & control, Endotoxins, Female, Fever, Formaldehyde, Hindlimb, Hyperalgesia, Injections, Intravenous, Isoenzymes, antagonists & inhibitors, metabolism, Isoxazoles, Ketorolac, toxicity, Male, Mice, Pain, Pain Measurement, Prostaglandin-Endoperoxide Synthases, Rats, Rats, Wistar, Stomach, drug effects, pathology

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          Abstract

          The antinociceptive, anti-inflammatory, antipyretic effects along with gastric safety profile of parecoxib, a novel, potent selective cyclooxygenase-2 inhibiting prodrug, and those of ketorolac, a nonselective cyclooxygenase inhibitor, were evaluated in various animal models. Parecoxib (up to 20 mg/kg, i.v.) had no effect in two acute pain models, namely, the acetic acid-induced writhing (visceral pain) and the formalin test (tonic pain). However, ketorolac (up to 10 mg/kg, i.v.) showed marked antinociceptive effects in these models. In the models of carrageenan-provoked inflammatory hyperalgesia and inflammation, and in lipopolysaccharide-induced pyrexia, parecoxib significantly reversed all the behavioral changes and it was found to be more potent than ketorolac. Further, ketorolac (10 mg/kg, i.v.) produced visible gastric lesions with prominent petechiae and hemorrhagic streaks. However, parecoxib was without any effect on gastric mucosa. The present results showed that the cyclooxygenase-2 inhibitor, parecoxib, when administered parenterally, has potent antihyperalgesic, anti-inflammatory, antipyretic effects and has a better safety profile than with ketorolac, with sparing of cyclooxygenase-1 in the stomach in these animal models.

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