NEW INSIGHTS INTO THE MODE OF ACTION OF ANTIINFLAMMATORY DRUGS

The discovery of a second cyclooxygenase has provided fresh impetus to the search for new antiinflammatory drugs. The second enzyme is effec tively absent from healthy tissues but its levels rise dramatically du ring inflammation. It can be induced in migratory cells by bacterial l ipopolysaccharide, cytokines and growth factors. The constitutive cycl ooxygenase-1 (COX-1) can thus be considered a ''housekeeping'' enzyme, in contrast to cyclooxygenase-2 (COX-2) which is activated by tissue damage. Both enzymes have a molecular weight of around 70 kDa and simi lar Km and Vmax values for their reaction with arachidonic acid. Sever al non steroid anti-inflammatory drugs which have more than 1,000 fold selectivity for COX-2 over COX-1 are in the early stages of drug deve lopment.