Spontaneous contractions of myometrium from humans, non-human primate and rodents are sensitive to selective oxytocin receptor antagonism in vitro

Objectives To determine whether: 1. oxytocin receptor antagonists influence spontaneous contractions of myometrium from humans, non-human primates and rodents (in vitro), and 2. vasopressin V-1a receptor antagonism is importa nt for inhibition of spontaneous contractions in human myometrium. Design In vitro pharmacology of spontaneous contractions of myometrium from humans and animals. Setting The research laboratories of a university department of obstetrics and gynaecology and a pharmaceutical industry research centre. Interventions Samples of human myometrium were obtained at caesarean sectio n. Tissue strips were suspended in organ baths for isometric force recordin g. Cumulative concentration effect curves to a selective oxytocin receptor antagonist (L-371,257) and a mixed oxytocin/vasopressin V-1a receptor antag onist (atosiban) were obtained. The effect of L-371,257 was also determined in myometrium from non-pregnant rats and marmosets. Main outcome measures The inhibition of spontaneous myometrial contractions in vitro. Results L-371,257 and atosiban significantly inhibited spontaneous activity of human myometrium in a concentration-related manner (P < 0.05), although the effect was more pronounced with L-371,257. Spontaneous contractions of myometrium from non-pregnant rats and marmosets were also inhibited by L-3 71,257 (atosiban was not tested). Conclusions Spontaneous contractions of myometrium from humans, marmosets a nd rats are, at least in part, dependent on oxytocin receptor activity, in vitro. L-371,257 and atosiban may be inverse agonists. Selective non-peptid e oxytocin receptor antagonists may be effective tocolytics.