Studies on the in vitro inhibition of prostaglandin synthetase by fenclorac (α, m-dichloro- p-cyclohexylphenylacetic acid) and indomethacin

Abstract

Analysis of the effect of a new nonsteroidal anti-inflammatory compound, fenclorac ( αm-di-chloro- p-cyclohexylphenylacetic acid), on prostaglandin biosynthesis in vitro has shown the drug to be a potent inhibitor of this enzyme system. Fenclorac was ten times as active as indomethacin in inhibiting prostaglandin synthesis in bovine seminal vesicle microsomes. Inhibition by fenclorac was not appreciably dependent upon preincubation of drug with enzyme for maximal activity, and was reversible by dilution. The inhibitory activity of indomethacin was time-dependent and not readily reversible. Kinetic analysis indicated that fenclorac is a competitive inhibitor of prostaglandin synthe- tase, irrespective of preincubation conditions, whereas indomethacin inhibits noncompetitively if pre- incubated with enzyme, and competitively in the absence of any preincubation. Both drugs protected or stabilized prostaglandin synthetase activity under extended preincubation conditions.