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.
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 KCl-, 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)EC(50) 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).


CONCLUSIONS
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.
Karadas
Baris
B
Department of Pharmacology, Cumhuriyet University School of Medicine, 58140 Sivas, Turkey.
Kaya
Tijen
T
Guvenal
Tevfik
T
Cetin
Meral
M
Divrik
Iclal
I
Cetin
Ali
A
D000328:Adult; D002585:Cesarean Section; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015237:Dinoprost / Q000494:pharmacology; D005260:Female; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008565:Membrane Proteins; D009215:Myometrium / Q000187:drug effects; D010121:Oxytocin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011247:Pregnancy; D011451:Prostaglandin-Endoperoxide Synthases; D013449:Sulfonamides / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
C106876:5,5-dimethyl-3-(3-fluorophenyl)-4-(4-methylsulfonyl)phenyl-2(5H)-furanone; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D007527:Isoenzymes; D008565:Membrane Proteins; D013449:Sulfonamides; D010121:Oxytocin; D011189:Potassium Chloride; D015237:Dinoprost; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C012655:nimesulide