Interpreting the clinical significance of the differential inhibition of cyclooxygenase-1 and cyclooxygenase-2.
The International Consensus Meeting on the Mode of Action of COX-2 Inhibition (ICMMAC) brought together 17 international experts in arthritis, gastroenterology and pharmacology on 5 6 December 1997. The meeting was convened to provide a definition of COX-2 specificity and to consider the clinical relevance of COX-2-specific agents. These compounds are a new class of drugs that specifically inhibit the enzyme COX-2 while having no effect on COX-1 across the whole therapeutic dose range. The objectives of the meeting were to review the currently available data regarding the roles and biology of COX-1 and COX-2, and to foster a consensus definition on COX-2 specificity. At the present time, no guidelines exist for the in vitro and in vivo assessment of COX specificity, and it was felt that consensus discussion might clarify some of these issues. The meeting also reviewed recent clinical data on COX-2-specific inhibitors. The following article reflects discussion at this meeting and provides a consensus definition of COX-2-specific inhibitors.
Brooks
P
P
Faculty of Health Sciences, University of Queensland, Herston, Australia.
Emery
P
P
Evans
J F
JF
Fenner
H
H
Hawkey
C J
CJ
Patrono
C
C
Smolen
J
J
Breedveld
F
F
Day
R
R
Dougados
M
M
Ehrich
E W
EW
Gijon-Baños
J
J
Kvien
T K
TK
Van Rijswijk
M H
MH
Warner
T
T
Zeidler
H
H
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001773:Blood Cells / Q000187:drug effects; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000502:physiology*; D013379:Substrate Specificity; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; C496511:PTGS1 protein, human; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases