In vivo
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Oxytocin antagonist (OTA), TT-235, was developed by our group and shown to inhibit either spontaneous or oxytocin-induced uterine contractions in primates. The purpose of the present study was to confirm the duration of TT-235 to block oxytocin-induced uterine contractions in estrous rats. In Experiment 1, the time-response of the three OTAs on uterine contractility was examined. ⋯ In Experiment 2, TT-235 induced a significant decrease (p<0.05) in oxytocin receptor number and binding affinity at both 0.5 and 4 hours compared with controls. Antag I and Antag II did not alter oxytocin receptor number or binding affinity significantly at each time point studied compared with controls. In conclusion, TT-235 may inhibit the uterine response to oxytocin by decreasing oxytocin receptor numbers and oxytocin binding affinity, which might explain the prolonged oxytocin antagonist activity of TT-235.