SALICYLAMIDE REVERSES THE ASPIRIN-ANTAGONISTIC EFFECT OF SALICYLIC-ACID ON RAT PLATELET CYCLOOXYGENASE

The antagonistic effect of salicylic acid (SA), the major metabolite o f aspirin, on aspirin (ASA)-induced inhibition of cyclooxygenase has b een recognized in vivo and in vitro. Salicylamide is available with as pirin in some analgesic preparations. Salicylamide shares important ch aracteristics with salicylic acid including the lack of effect on cycl ooxygenase and platelet aggregation as well as a close structural rese mblance. This prompted us to study the interaction of salicylamide wit h aspirin and/or SA on rat platelet and cyclooxygenase. Our results sh owed that salicylamide has, unlike SA, no blocking effect on the anti- cyclooxygenase effect of aspirin in vitro. Moreover, salicylamide coul d dose-dependently prevent the aspirin-blocking effect of SA on platel et cyclooxygenase. These results suggest that salicylamide and SA comp ete for a receptor on cyclooxygenase different to that of aspirin. A f unctional model of cyclooxygenase enzyme is proposed.