Comparison of the effects of nimesulide and 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanone (DFU) on contractions of isolated pregnant human myometrium

Abstract

Objective: To compare the effects of 5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulphonyl) phenyl-2(5H)-furanone (DFU) and nimesulide, selective COX-2 inhibitors, on the amplitude and frequency of KCI-, oxytocin-, and PGF(2alpha)-stimulated contractions of isolated pregnant human myometrial strips. Methods: Isolated myometrial strips were obtained from 20 pregnant women undergoing elective cesarean section. These strips were mounted in organ baths for recording of isometric tension. The effects of cumulative concentrations of nimesulide and DFU on KCl-, oxytocin-, and PGF(2alpha)-stimulated myometrial contractions were measured, and values for -log(10) EC50 and mean maximal inhibition (E-max) were compared. Nimesulide (10(-8) to 10(-4) M) and DFU (10(-8) to 10(-4) M) inhibited in a concentration-dependent manner the KCl-, oxytocin-, and PGF(2alpha)-stimulated contractions of myometrial strips, with a significant effect on the amplitude (10(-7) to 10(-4) M) and the frequency (10(-6) to 10(-4) M). Results: The inhibitor effect of DFU was more potent than nimesulide on KCl-, oxytocin-, and PGF(2alpha)-stimulated myometrial contractions, however, the inhibitor effects of nimesulide and DFU was much greater on KCl-stimulated contractions than on oxytocin- and PGF(2alpha)-stimulated myometrial contractions (P < 0.05). There was no significant difference between E-max values of nimesulide and DFU in all tissues (P > 0.05). Conclusion: DFU is a more potent inhibitor than nimesulide on KCl-, oxytocin-, and PGF(2alpha)-stimulated contractions of pregnant human myometrium. The inhibitor effects of nimesulide and DFU were predominantly on KCl-stimulated contractions. (C) 2003 Elsevier Ireland Ltd. All rights reserved.