Morphine Inhibits Nocturnal Oxytocin Secretion and Uterine Contractions in the Pregnant Baboon1

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Morphine is a potent inhibitor of nocturnal uterine contractions (UCs) in the pregnant baboon, and these contractions are known to be induced by oxytocin (OT). The purpose of this study was to determine the mode of action of morphine in inhibiting nocturnal UCs by examining the effect of morphine on OT secretion, OT clearance, and uterine responsiveness to OT. A tethered pregnant baboon model during the last third of gestation was used for these experiments. In study 1, the effects of morphine or control saline on OT release and on spontaneous nocturnal UCs were examined. Study 2 determined the effects of morphine or control saline on the pharmacokinetics of OT after a bolus injection of OT. To exclude/include direct opiate effects on UCs, study 3 examined the responsiveness of the uterus to exogenous OT after morphine or control saline administration. Plasma OT levels were analyzed by RIA after extraction. UCs were assessed by frequency, amplitude, duration, and area under the curve.

During nocturnal UCs, morphine, but not saline, administration resulted in the precipitous suppression of integrated OT levels (p < 0.05) to 42% of pretreatment values at 0-15 min postinjection and 17% at 30-45 min. Simultaneously, UCs were significantly suppressed (p < 0.05) by 75% at the 30- to 45-min interval. By 1 h, 5 of 7 animals showed no UCs. In study 2, morphine consistently increased the metabolic clearance rate (MCR) of OT in all trials (p < 0.05), although the magnitude of this effect was small (median 9%). Finally, study 3 demonstrated that myometrial responsiveness to the challenge of exogenous OT was not depressed by opiate administration (p > 0.05). To summarize, the decrease in nocturnal UCs after morphine is primarily due to an inhibition of OT release, and perhaps, but to a much lesser extent, an increase in OT MCR. There was no evidence of a direct tocolytic effect of morphine on the uterus. In conclusion, opioids such as morphine are potent inhibitors of nocturnal UCs and act by suppressing OT release in the pregnant baboon.

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