Vasotocin analogues which competitively inhibit vasopressin stimulated uterine activity in healthy women.
Three analogues of posterior pituitary hormones, 1-deamino-2-D-Tyr(OEt)-4-Val-8-Orn-vasotocin(dE-VVT), 1-deamino-2-D-Tyr(OEt)-4-Thr-8-Orn-vasotocin(dE-TVT) and 1-deamino-2-D-Tyr(OEt)-oxytocin(dE-OXY) were compared for their inhibitory effects on vasopressin (VP)-induced uterine activity in healthy women. At menstruation, during recording of intrauterine pressure (18 recording sessions in 11 women), intravenous infusion of lysine vasopressin (LVP, 1 ng/min/kg/body weight) induced an increase of the uterine activity and dysmenorrhoea-like symptoms. Intravenous injections of all analogues (10 micrograms/kg body weight) caused relief of symptoms and inhibition of uterine activity, dE-TVT was the most effective and dE-OXY was least active. With dE-TVT almost complete inhibition of contractions was seen during the first 10 min after injection. The duration of effect was also greatest with that analogue (40-50 min). Only dE-OXY had an agonist effect on spontaneous uterine activity. Pharmacokinetic studies of intravenous dE-TVT (10 ng/kg body weight) showed that the plasma half-life was approximately 16 min and the clearance 30 l/h. The bioavailability of 100 ng/kg given intranasally was about 5.5%. Further studies are recommended.
D000328:Adult; D001682:Biological Availability; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007700:Kinetics; D008236:Lypressin / Q000494:pharmacology; D008297:Male; D008598:Menstruation / Q000187:drug effects; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014590:Uterine Contraction / Q000187:drug effects; D014599:Uterus / Q000187:drug effects*; D014668:Vasotocin / Q000031:analogs & derivatives* / Q000494:pharmacology
C047046:atosiban; C047045:vasotocin, 1-desamino-OEt-Tyr(2)-Val(4)-Orn(8)-; D010121:Oxytocin; D008236:Lypressin; C038782:oxytocin, 1-desamino-(O-Et-Tyr)(2)-; D014668:Vasotocin