Journal
BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY
Volume 110, Issue 11, Pages 1025-1028Publisher
ELSEVIER SCIENCE BV
DOI: 10.1111/j.1471-0528.2003.02540.x
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Objective To compare a newly developed oxytocin antagonist, FE 200 440, with atosiban and ANTAG III, as to potency and selectivity of inhibitory effects on oxytocin- and vasopressin-induced myometrial responses. FE 200 440 has high affinity for the human cloned oxytocin receptor, approximately 300-fold that for the vasopressin V-1a receptor, whereas atosiban binds well to both receptors. Design In vitro study of human myometrial contractility. Setting The Research Laboratory of the Department of Obstetrics and Gynecology, Lund University Hospital, Sweden. Participants Forty-seven term-pregnant women not in labour who were delivered by caesarean section. Interventions Concentration-response curves with oxytocin and arginine vasopressin on isolated myometrial strips were recorded in control experiments, in the presence of atosiban in concentrations of 25, 250 and 750 nmol/L, and after pretreatment with ANTAG III and FE 200 440, both in concentrations of 2.5, 25 and 250 nmol/L. Main outcome measure pA(2) values (i.e. an index of inhibitory action). Results With oxytocin as the agonist, the median pA(2) values for atosiban, ANTAG III and FE 200 440 were 10.6, 9.5 and 8.3, respectively. With vasopressin as the agonist, the pA(2) values for atosiban and ANTAG III were 8.8 and 8.7, whereas no inhibitory effect of FE 200 440 was seen in five out of six experiments. Conclusion The new analogue FE 200 440 is a selective oxytocin antagonist and, in contrast to atosiban and ANTAG III, has practically no effect on vasopressin-induced contractions of isolated term-pregnant human myometrium.
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