Inhibition of cyclooxygenase-1 and -2 by R(-)- and S(+)-ibuprofen.
Since the discovery of a cytokine-inducible isozyme of cyclooxygenase (COX-2), its pharmacologic inhibition has been the subject of recent investigations. These include tests for the selectivity of known nonsteroidal antiinflammatory drugs (NSAIDs) on the constitutive enzyme of cyclooxygenase (COX-1) compared with the inducible enzyme COX-2. The interesting question arose whether the R(-)- and S(+)-isomers exhibited different inhibitory potencies for ibuprofen. Results with isolated COX-1 and COX-2 isozymes confirmed the known higher efficacy of S(+)-compared with R(-)-ibuprofen. The R(-)-isomer is almost inactive in inhibiting COX-2. In addition, the S(+) form has a several times lower potency with COX-2 than with COX-1. These data were evaluated in platelets containing mainly the constitutive COX-1, with interleukin-1, pretreated, rat mesangial cells which almost exclusively express COX-2.
Boneberg
E M
EM
Faculty of Biology, University of Konstanz, Germany.
Zou
M H
MH
Ullrich
V
V
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D006801:Humans; D007052:Ibuprofen / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D051381:Rats; D013237:Stereoisomerism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D007052:Ibuprofen