Inhibition of oxytocin-induced uterine contractions by an oxytocin antagonist in the pregnant baboon.

Uterine contractions were induced with oxytocin in anesthetized pregnant baboons (Papio anubis) at three stages of pregnancy (days 140, 156, and 169; normal gestation length, 184 days). After the contractile activity was greater than two to three contractions every 10 minutes, beta-mercapto-beta, beta-cyclopentamethylenepropionic acid1-[D-Trp2,Phe3,Ile4,Arg8]-oxytocin, a novel oxytocin antagonist produced in our laboratories, was given simultaneously with the oxytocin for 90 minutes. Contractile force (frequency x mean amplitude) was determined for 30 minutes before and for three 30-minute intervals after the oxytocin antagonist was administered. Animals at 140 days' gestation showed a significant (p less than 0.05) decrease in contractile force in the first 30-minute interval after oxytocin antagonist infusion was initiated, whereas those at days 156 and 169 showed decreases (p less than 0.05) at the second 30-minute interval. In addition, in late gestation a higher dose of oxytocin antagonist per unit of oxytocin was required to prevent uterine contractions. In conclusion, these results suggest (1) that an oxytocin antagonist can inhibit oxytocin-induced uterine contractions in the pregnant baboon and (2) that the interval from oxytocin antagonist administration to significant inhibition of uterine contractions appears to increase with advancing gestational age.