Pharmacological profile of celecoxib, a specific cyclooxygenase-2 inhibitor.
The pharmacological profile of celecoxib (CAS 169590-42-5, SC-58635), a specific cyclooxygenase-2 (COX-2) inhibitor, was investigated. Celecoxib inhibited COX-2-mediated prostaglandin E2 (PGE2) production in human dermal fibroblasts (IC50 = 91 nmol/l), whereas it was a weak inhibitor of COX-1-mediated PGE2 production in human lymphoma cells (IC50 = 2800 nmol/l). In in vivo studies, the effects of celecoxib were compared with those of nonsteroidal anti-inflammatory drugs (NSAIDs) in acute rat models of hyperalgesia and pyrexia. Celecoxib abrogated carrageenan-induced hyperalgesia in the hind paw accompanied by a decrease in PGE2 content in paw exudates and cerebrospinal fluid in a dose-related manner, with an ED30 = 0.81 mg/kg. Its analgesic potency was comparable to those of NSAIDs. In lipopolysaccharide-induced pyrexia, the anti-pyretic potency of celecoxib was equal to that of NSAIDs. On the other hand, in a gastric toxicity study in rats, single oral administration of celecoxib had no effect on gastric mucosa or mucosal PGE2 content at doses up to 200 mg/kg. Additionally, celecoxib did not inhibit thromboxane B2 production of calcium ionophore-stimulated peripheral blood of rats or arachidonic acid-induced aggregation of human platelets. These findings suggest that celecoxib might be a safe and effective alternative to NSAIDs for clinical use.
Yoshino
Taiji
T
Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Kimoto
Aishi
A
Kobayashi
Seiji
S
Noguchi
Masahiro
M
Fukunaga
Masahiro
M
Hayashi
Asuka
A
Miyata
Keiji
K
Sasamata
Masao
M
D000818:Animals; D002351:Carrageenan; D000068579:Celecoxib; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D005334:Fever / Q000139:chemically induced / Q000188:drug therapy; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000494:pharmacology; D008070:Lipopolysaccharides; D008223:Lymphoma / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000139:chemically induced / Q000473:pathology; D013449:Sulfonamides / Q000494:pharmacology*; D013929:Thromboxane B2 / Q000096:biosynthesis; D014407:Tumor Cells, Cultured
D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007375:Interleukin-1; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011720:Pyrazoles; D013449:Sulfonamides; D013929:Thromboxane B2; D002351:Carrageenan; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C496513:Ptgs1 protein, rat; D000068579:Celecoxib; D015232:Dinoprostone