TY - JOUR
T1 - Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain
AU - Seibert, Karen
AU - Zhang, Yan
AU - Leahy, Kathleen
AU - Hauser, Scott
AU - Masferrer, Jaime
AU - Perkins, William
AU - Lee, Len
AU - Isakson, Peter
PY - 1994/12/6
Y1 - 1994/12/6
N2 - Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used for the treatment of inflammatory diseases, but significant side effects such as gastrointestinal erosion and renal damage limit their use. NSAIDs inhibit the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to prostaglandins (PGs) and thromboxane. Two forms of COX have been identified-COX-1, which is constitutively expressed in most tissues and organs, and the inducible enzyme, COX-2, which has been localized primarily to inflammatory cells and tissues. In an animal model of acute inflammation (injection of carrageenan into the footpad), edema was produced that was associated with marked accumulation of COX-2 mRNA and thromboxane. A selective inhibitor of COX-2 (SC-58125) inhibited edema at the inflammatory site and was analgesic but had no effect on PG production in the stomach and did not cause gastric toxicity. These data suggest that selective inhibition of COX-2 may produce superior antiinflammatory drugs with substantial safety advantages over existing NSAIDs.
AB - Nonsteroidal antiinflammatory drugs (NSAIDs) are widely used for the treatment of inflammatory diseases, but significant side effects such as gastrointestinal erosion and renal damage limit their use. NSAIDs inhibit the enzyme cyclooxygenase (COX), which catalyzes the conversion of arachidonic acid to prostaglandins (PGs) and thromboxane. Two forms of COX have been identified-COX-1, which is constitutively expressed in most tissues and organs, and the inducible enzyme, COX-2, which has been localized primarily to inflammatory cells and tissues. In an animal model of acute inflammation (injection of carrageenan into the footpad), edema was produced that was associated with marked accumulation of COX-2 mRNA and thromboxane. A selective inhibitor of COX-2 (SC-58125) inhibited edema at the inflammatory site and was analgesic but had no effect on PG production in the stomach and did not cause gastric toxicity. These data suggest that selective inhibition of COX-2 may produce superior antiinflammatory drugs with substantial safety advantages over existing NSAIDs.
KW - hyperalgesia
KW - nonsteroidal antiinflammatory drug
KW - prostaglandin
UR - http://www.scopus.com/inward/record.url?scp=0027944075&partnerID=8YFLogxK
U2 - 10.1073/pnas.91.25.12013
DO - 10.1073/pnas.91.25.12013
M3 - Article
C2 - 7991575
AN - SCOPUS:0027944075
SN - 0027-8424
VL - 91
SP - 12013
EP - 12017
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 25
ER -