title: The effect on the human uterus of two newly developed competitive inhibitors of oxytocin and vasopressin.
abstract: In order to develop inhibitors of vasopressin (VP) and oxytocin (OXY) action on uterine activity, 1-deaminated vasotocin derivatives with modifications at positions 2, 4 and 8 were developed. Two of the most effective analogues in the rat, 1-deamino-2-D-Tyr(OEt)-4-Val-8-Orn-vasotocin (dE-VVT) and 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin (dE-TVT) were now tested on human nonpregnant myometrium obtained at hysterectomy in fertile age and on pregnant myometrial tissue obtained at elective cesarean section. The effect was compared with that of a previously synthesized analogue 1-deamino-Tyr(OEt)-oxytocin (dE-OXY) which has already been tested in nonpregnant and pregnant women in vivo. Both of the new analogues competitively inhibited the action of the posterior pituitary hormones. On the nonpregnant uterus dE-VVT was about five times and dE-TVT almost twenty-five times more potent than dE-OXY in inhibiting the effects of VP. On pregnant myometrium, dE-TVT inhibited oxytocin action about as effectively as a five-fold stronger concentration of dE-OXY, and dE-VVT slightly less. A moderate agonistic effect of dE-OXY on pregnant myometrium was found, whereas it was minimal with dE-VVT and not detectable at all with dE-TVT. It appears that these two analogues, particularly dE-TVT, would be interesting for clinical testing both in dysmenorrhea, where increased VP secretion could be of etiological importance, and in premature labor where an increased myometrial concentration of OXY receptors has been demonstrated.
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009215:Myometrium / Q000187:drug effects; D010121:Oxytocin / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D011247:Pregnancy; D014590:Uterine Contraction / Q000187:drug effects*; D014667:Vasopressins / Q000037:antagonists & inhibitors*; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: C047046:atosiban; D014667:Vasopressins; C047045:vasotocin, 1-desamino-OEt-Tyr(2)-Val(4)-Orn(8)-; D010121:Oxytocin; C038782:oxytocin, 1-desamino-(O-Et-Tyr)(2)-; D014668:Vasotocin