Inhibition of prostaglandin synthase by pirprofen. Studies with sheep seminal vesicle enzyme

Abstract

1. Pirprofen, racemic 2-[3-chloro-4(3-pyrrolinyl) phenyl] propionic acid, was evaluated for its ability to inhibit the conversion of arachidonic acid into prostaglandin E2 by sheep seminal vesicle prostaglandin synthase in vitro. 2. The compound proved to be a potent inhibitor with a Ki value of about 1.2 muM. Like indomethacin, aspirin and certain other non-steroidal anti-inflammatory drugs, pirprofen inhibited the enzyme competively with respect to substrate. Unlike most non-steroidal anti-inflammatory drugs, however, pirprofen did not promote time-dependent inactivation of the enzyme. It behaved as a competitive, reversible inhibitor, whereas most of the other agents acted as competitive, irreversible inhibitors. 3. The results suggest that inhibition of prostaglandin synthesis accounts in large part for the pharmacological effects of pirprofen.