Pharmacological profile of parecoxib: a novel, potent injectable selective cyclooxygenase-2 inhibitor.
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.
Padi
Satyanarayana S V
SS
Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh 160014, India.
Jain
Naveen K
NK
Singh
Sukhjeet
S
Kulkarni
Shrinivas K
SK
D019342:Acetic Acid; D000818:Animals; D002351:Carrageenan; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004487:Edema / Q000139:chemically induced / Q000517:prevention & control; D004731:Endotoxins; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D005557:Formaldehyde; D006614:Hindlimb; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control; D007275:Injections, Intravenous; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007555:Isoxazoles / Q000494:pharmacology*; D020910:Ketorolac / Q000494:pharmacology / Q000633:toxicity; D008297:Male; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control; D010147:Pain Measurement; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects / Q000473:pathology
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D004731:Endotoxins; D007527:Isoenzymes; D007555:Isoxazoles; D005557:Formaldehyde; D002351:Carrageenan; C409945:parecoxib; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D019342:Acetic Acid; D020910:Ketorolac