Pharmacological Profile of Celecoxib, a Specific Cyclooxygenase-2 Inhibitor

Abstract

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.

IL-1β Suppresses the Formation of Osteoclasts by Increasing OPG Production via an Autocrine Mechanism Involving Celecoxib-Related Prostaglandins in Chondrocytes

“…Therefore, we focused on the formation of osteoclasts via the RANK/RANKL/OPG system that communicates between osteoclast precursors and chondrocytes. This study was performed to clarify the effect of IL-1 β and/or celecoxib, a specific inhibitor of COX-2 [24, 25], on the expression of M-CSF, RANKL, and OPG in human chondrocytes, and the indirect effect of IL-1 β on the formation of osteoclast-like cells using RAW264.7 cells as osteoclast precursors. The chondrocytes used in this study strongly expressed type II collagen and aggrecan, which is the common phenotype expressed by proliferating chondrocytes and hypertrophic chondrocytes; whereas the expression of type X collagen, which is the phenotype expressed by hypertrophic chondrocytes, was very low in the cells (data not shown).…”

“…The celecoxib concentration used in this study was decided based on the report of Itthipanichpong et al [25], who examined the blood level after injecting celecoxib, and our previous study, which found that IL-1 β increases the production of PGE 2 , COX-2, and EP4 receptor in the same chondrocytes as used in this study [23]. Celecoxib specifically inhibits COX-2 [24, 25]. We have already confirmed that 1  μ M celecoxib blocked PGE 2 production by inhibiting COX-2 in 100 U/mL IL-1 β -stimulated chondrocytes [23].…”

“…For this reason, we examined the effects of IL-1 β and celecoxib, a specific inhibitor of COX-2 [24, 25], on the expression of M-CSF, RANKL, and OPG in human chondrocytes, and the indirect effect of IL-1 β on the formation of osteoclast-like cells using RAW264.7 cells as osteoclast precursors.…”

The importance of cyclooxygenase 2-mediated oxidative stress in obesity-induced muscular insulin resistance in high-fat-fed rats

“…The effective doses of drugs were chosen as described in previous studies (Hsieh et al, 2008;Yoshino et al, 2005;Liu et al, 2009).…”

Comparative study of the clinical efficacy of the selective cyclooxygenase-2 inhibitor celecoxib compared with loxoprofen in patients with frozen shoulder

“…Celecoxib is a novel anti-inflammatory and analgesic drug of the coxib family that selectively inhibits COX-2, and shows stronger inhibitory activity against COX-2 than COX-1 [2,3]. Japanese and overseas studies suggested that the incidence and severity of upper gastrointestinal disorders induced by celecoxib were lower than those induced by existing NSAIDs [4][5][6][7][8][9].…”