Inhibition of Cyclooxygenase‐1 and ‐2 by R(‐)‐ and S(+)‐Ibuprofen

Abstract

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.