Studies of the effects of subacute treatment with N‐(cyclopropylmethyl)−19‐isopentylnororvinol (M320) on timing of parturition in the rat

Abstract

1 Administration of 10ojgkg-' of the long lasting potent K-and weaker i-opioid agonist N-(cyclopropylmethyl)-19-isopentylnororvinol (M320) twice daily from day 20 of gestation prolonged the internal gestation period of the rat and retarded the development of the offspring in the perinatal period. 2 The capacities of myometrial, placental and cervical tissues to produce prostaglandin E2 (PGE2) were not affected by M320 treatment. 3 During the period in which parturition normally occurred in saline-treated rats, foetal pituitary levels of immunoreactive oxytocin (ir-OXY) but not immunoreactive arginine-vasopressin (ir-AVP) were greater in M320-compared to saline-treated animals. Following the completion of parturition, foetal pituitary ir-OXY and ir-AVP levels continued to rise in saline-treated rats, but fell dramatically in rats treated subacutely with M320. 4 These data indicate that subacute treatment with M320 may inhibit foetal oxytocin release at term. This foetal OXY release may be a stimulus for the initiation of labour.

Effects of Subacute Opioid Administration During Late Pregnancy in the Rat on the Initiation, Duration and Outcome of Parturition and Maternal Levels of Oxytocin and Arginine Vasopressin

“…Subacute M320 administration may be accompanied by reduced fetal OXY release at term (Evans et al 1988). The maternal release of OXY and AVP before, during and after parturition, and its modulation by subacute administration of M320 was therefore investigated.…”

“…There is, however, some evidence that changes in the sensitivity of the neurohypophysis t o the inhibitory effects ofopioids occur around the time of parturition in rats . Furthermore, subacute M320 treatment may inhibit fetal OXY release at term (Evans et a/. 1988), indicating that at least the fetal neurohypophysis may not become tolerant to the inhibitory effects of M320 after subacute treatment.…”

“…Blood was collected into chilled heparinized tubes and the plasma separated after centrifugation (2000 r/min) for 15 min at 4°C (Clements GS2000). Plasma was stored at -20°C until extraction with acetone/hexane (2 mL acetone, 3 mL hexane) and radio-immunoassay of OXY (Rice & Thorburn 1985;Evans et al 1988) and AVP (Woods & Johnston 1983) were performed. Whole maternal pituitary glands were removed and stored at -20°C in 0.5 mL of 0.1 mol/L HCI until extraction and assay of OXY and AVP (Evans et al 1988) occurred.…”

“…While this action does not appear to involve modulation of myornetrial, cervical or placental prostaglandin E2 synthesis, it may involve inhibition of fetal oxytocin (OXY) release (Evans et al 1988). …”

“…Subacute administration, to Long-Evans rats during late pregnancy, of the potent and long lasting K-and p-opiate receptor agonist N-(cyclopropylmethyl)-19-isopentylnororvino1 (M320) (Boura & Fitzgerald 1966;Abrahams et al 1986) delays the initiation of parturition (Evans et al 1987a;Evans et al 1988). While this action does not appear to involve modulation of myornetrial, cervical or placental prostaglandin E2 synthesis, it may involve inhibition of fetal oxytocin (OXY) release (Evans et al 1988).…”