Tocolytic Effect of Morphine via Increased Metabolic Clearance of Oxytocin in the Baboon

Morphine is known to inhibit nocturnal uterine contractions in several animal models, and oxytocin is known to be a primary causative factor of uterine contractions. The purpose of the present study was to determine the tocolytic effect of morphine in relation to the pharmacokinetics of oxytocin, after a bolus injection of oxytocin. The metabolism of oxytocin was investigated during the third trimester in baboons. Four animals were placed on a tether system with venous and arterial access, including continuous uterine monitoring. Plasma oxytocin levels were determined by radioimmunoassay after extraction with petroleum ether/acetone. Morphine consistently increased the metabolic clearance rate of oxytocin in all four animals (p < 0.05) and this was in accordance with suppressed uterine contractions. We conclude that morphine could be used as an inhibitor of nocturnal uterine contractions, and that this is caused by the morphine induced increased metabolic clearance rate of oxytocin.

The effect of oxytocin antagonist on uterus in response to exogenous oxytocin

This study was performed to determine the action mode of oxytocin antagonist. In Study 1, the duration of in vivo action of oxytocin antagonist I (AI) was examined. After infusing AI, oxytocin was given and repeated every hour for 5 hr. Uterine activities were monitored with a polygraph. Study 2 determined the effect of AI on uterine oxytocin receptor number (Rn) and binding affinity (Kd). AI treated rats were sacrificed at 0.5 and 4 hr later for receptor assay. In Study 1, the uterine contractile response to oxytocin was significantly inhibited (p>0.05) compared to controls at five min, 1 and 2 hr after injection of AI. No differences in response were detected compared to controls (p>0.05) at later hours. In Study 2, no differences (p>0.05) between the AI and control animals in either oxytocin receptor number or binding affinity was found. These data suggest that the major mode of AI action is via competitive inhibition at the uterine oxytocin receptor and not by altering receptor number or binding affinity. AI is suggested to have the potential of being a potent and specific tocolytic agent for prevention of preterm labor in human.

The effect of oxytocin antagonist on uterus in response to exogenous oxytocin

This study was performed to determine the action mode of oxytocin antagonist. In Study 1, the duration of in vivo action of oxytocin antagonist I (AI) was examined. After infusing AI, oxytocin was given and repeated every hour for 5 hr. Uterine activities were monitored with a polygraph. Study 2 determined the effect of AI on uterine oxytocin receptor number (Rn) and binding affinity (Kd). AI treated rats were sacrificed at 0.5 and 4 hr later for receptor assay. In Study 1, the uterine contractile response to oxytocin was significantly inhibited (p>0.05) compared to controls at five min, 1 and 2 hr after injection of AI. No differences in response were detected compared to controls (p>0.05) at later hours. In Study 2, no differences (p>0.05) between the AI and control animals in either oxytocin receptor number or binding affinity was found. These data suggest that the major mode of AI action is via competitive inhibition at the uterine oxytocin receptor and not by altering receptor number or binding affinity. AI is suggested to have the potential of being a potent and specific tocolytic agent for prevention of preterm labor in human.