Potential use of oxytocin and vasopressin V1a antagonists in the treatment of preterm labour and primary dysmenorrhoea.

In order to study the involvement of oxytocin (OT) and vasopressin (AVP) in mechanisms of uterine activation and to clarify the therapeutic potential of antagonists to these hormones in preterm labour and primary dysmenorrhoea, studies of human uterine contractility in vivo and in vitro as well as measurements of OT and AVP V1a receptors were performed. Good correlations between OT receptor concentrations and effects on contractility were observed in both the pregnant and non-pregnant states, which indicates that OT acts specifically on its own receptor in the uterus. For AVP there was lack of such correlation which may suggest that this hormone influences both the OT and AVP V1a receptor sites. At the onset of labour both preterm and at term no marked increase in the OT receptor concentration was observed, but OT may still be involved in the initiation of labour, being produced locally in the uterus and not detectable in plasma. We observed a reduced OT receptor concentration in advanced labour and after OT infusion, which suggests that OT influences its own receptor. The AVP V1a receptor concentration and the effect of AVP on the uterus were about equal to those for OT, and the concentration of AVP V1a receptors also tended to decrease in advanced labour, observations which support an involvement also of AVP in the mechanisms of labour. In non-pregnant women AVP receptors as well as uterine effects of AVP in vitro and in vivo were about five times higher than those for OT, and the effect of AVP was increased premenstrually. This firmly supports an aetiological role of this peptide in the uterine hyperactivity of primary dysmenorrhoea. We have also shown that the analogue 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-OT, which blocks both the OT and AVP V1a receptor sites, given by intravenous infusion inhibits both preterm labour and dysmenorrhoea, and this is in agreement with our receptor and contractility findings.