AJP - Regulatory, Integrative and Comparative Physiology, Vol 261, Issue 2 358-R368, Copyright © 1991 by American Physiological Society
Pethidine (meperidine) inhibition of oxytocin secretion and action in parturient rats
J. A. Russell, G. Leng, J. E. Coombes, S. A. Crockett, A. J. Douglas, I. Murray and S. Way
Department of Physiology, Medical School, Edinburgh University, United Kingdom.
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.
