Tocolytic effect of parecoxib, a new parenteral cyclo-oxygenase-2-specific inhibitor, on the spontaneous and prostaglandin-induced contractions of rat isolated myometrium.
1. The present study was undertaken to elucidate the effects of parecoxib, a novel cyclo-oxygenase (COX)-2 inhibitor, on spontaneous and prostaglandin-induced contractions of uterine smooth muscle. 2. Non-pregnant adult Wistar rats were decapitated and dissected to isolate myometrial strips. The tissue was mounted in 5 mL organ baths filled with Krebs' solution that was maintained at 37 degrees C and bubbled continuously with a mixture of 95% O(2)-5% CO(2) to give pH 7.4. Contractions were recorded through transducers for isometric tension recording. The dose-dependent effects of parecoxib on contractility were quantified by changes in the mean amplitude, frequency and area under the contractile curve (AUC; percentage of control conditions) of the isometric tension recordings, averaged over 5 min intervals. Statistical analyses were performed using ANOVA. 3. Application of parecoxib (50-900 micromol/L) caused dose-dependent decreases in mean amplitude, mean frequency and mean AUC of both spontaneous and prostaglandin-induced contractions. Mean percentage inhibition of the AUC of spontaneous contractions was found to be 29, 56, 74 and 84% in the presence of 50, 150, 300 and 600 micromol/L parecoxib, resepctively (n = 8). In the case of prostaglandin (PG) F(2alpha)-induced contractions, 100, 300, 600 and 900 micromol/L parecoxib resulted in a 27, 43, 61 and 73% inhibition, respectively (n = 9). Moreover, pretreatment with parecoxib (600 micromol/L) reduced the responsiveness and maximum contractility to PGF(2alpha) compared with non-treated strips. 4. The data from the present study indicate, for the first time, that parecoxib inhibits spontaneous and prostaglandin-induced contractions of rat myometrium in vitro. These results raise the possibility that parecoxib may be of therapeutic use in the management of preterm labour and dysmenorrhoea.
Ayar
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Department of Physiology, Faculty of Medicine, Firat University, Elazig, Turkey. aayar61@yahoo.com
D000818:Animals; D019540:Area Under Curve; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D015237:Dinoprost / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D007555:Isoxazoles / Q000494:pharmacology*; D009215:Myometrium / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D015149:Tocolytic Agents / Q000494:pharmacology*; D014590:Uterine Contraction / Q000187:drug effects*
D052246:Cyclooxygenase 2 Inhibitors; D007555:Isoxazoles; D015149:Tocolytic Agents; C409945:parecoxib; D015237:Dinoprost; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat