Vasotocin analogues which competitively inhibit vasopressin stimulated uterine activity in healthy women

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Abstract
Summary. Three analogues of posterior pituitary hormones, 1 ‐ deamino ‐ 2 ‐ D ‐ Tyr(OEt) ‐ 4 ‐ Val ‐ 8 ‐ Om ‐ vasotocin(dE ‐ VVT), l‐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 μg/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 1/h. The bioavailability of 100 ng/kg given intra‐nasally was about 5·5%. Further studies are recommended.