Pethidine (meperidine) inhibition of oxytocin secretion and action in parturient rats

Abstract

Pethidine (also known as meperidine and as Demerol) injected subcutaneously at 10 mg/kg into parturient rats on the birth of the second pup resulted in a marked slowing of the progress of parturition, associated with reduced plasma oxytocin concentrations. Injection of the opiate antagonist naloxone counteracted the inhibition of oxytocin secretion and largely prevented the slowing of parturition. In vitro, pethidine inhibited spontaneous, oxytocin-induced and acetylcholine-induced contractions of uteri from rats immediately post partum, and these effects were not reversed by naloxone. In anesthetized lactating rats, pethidine inhibited the suckling-induced milk-ejection reflex and attenuated oxytocin-induced contractions of mammary myoepithelium. Finally, pethidine depressed plasma oxytocin concentrations in rats given 2% saline to drink for 24 h to stimulate oxytocin secretion. Thus pethidine inhibits oxytocin secretion in all three conditions; this inhibition is probably mediated by central opioid receptors. In addition, however, pethidine depresses the oxytocin responsiveness both of mammary myoepithelium and of myometrium. The latter effect at least is not opioid mediated.

Efficacy and Effects of Parenteral Pethidine or Meptazinol and Regional Analgesia for Pain Relief during Delivery. A Comparative Observational Study

“…The differences be- tween pethidine and meptazinol postulated in other studies with regard to postnatal Apgar scores [16], maternal nausea and emesis [23] and inhibitory effect on oxytocin secretion [24,25] were not found in our study. Only postnatal umbilical cord arterial pH was found to be lower following pethidine therapy, although the averages for both opioids were within normal ranges and the difference was therefore not clinically relevant.…”

Effects of the κ‐opioid agonist U50,488 on parturition in rats

“…In a second experiment, to test lower doses of opioids and reversibility by the c-selective antagonist, norbinaltorphimine (norBNI), early on day 20 of pregnancy rats were anaesthetized with ether and a cannula was inserted into a jugular vein and led subcutaneously to the back of the neck and exteriorized (see Russell et al, 1991); the cannula was occluded with a stainless steel wire, withdrawn the next day when the cannula was connected via a length of tubing to a syringe for later drug injection without disturbance during parturition. Intravenous injections were given 1 and 6 min after the birth of the second pup as follows: either vehicle (0.9% saline 0.5 ml kg-'), then vehicle again, or vehicle then U50,488 (1 mg kg-'), or norBNI (0.5 mg kg-') then U50,488 (1 mg kg-') or vehicle then morphine (1 mg kg-'), or norBNI (0.5 mg kg-') then morphine (1 mg kg-').…”

Endogenous opioid regulation of oxytocin release during parturition is reduced in ovariectomized rats

“…In ovariectomized steroid-treated rats parturition was prolonged compared with sham-ovariectomized rats, regardless of whether progesterone was removed on day 20 or day 21 of pregnancy, and despite normal plasma oxytocin concentrations at the birth of pup 2 compared with those in intact rats. Furthermore, the increase in oxytocin secretion following naloxone did not restore normal parturi¬ tion, unlike its actions on parturition disrupted either by stress or by the administration of exogenous opioids (Russell et al , 1991. As the disruption of parturition in ovariectomized rats could not be overcome by increasing circulating oxytocin concentrations to above the levels seen in sponta¬ neous parturition, it is unlikely that the disruption is related only to an inhibition of central control of oxytocin secretion but is probably due to the effect of the absence of relaxin on the preparation of the birth canal for parturition; relaxin induces marked softening and extensibility of the cervix (Downing & Sherwood, 1985a), and induces elongation of the pubic ligament (Hisaw & Zarrow, 1950).…”