Retosiban

Retosiban (GSK221149A) is a potent, selective, and orally active oxytocin receptor antagonist (K_i (hOT) = 0.65 nM, K_i (rOT) = 4.1 nM) with no detectable agonist activity. Retosiban has nanomolar affinity for the oxytocin receptor with >1400-fold selectivity over the closely related vasopressin receptors. Retosiban inhibits spontaneous and induces uterine contractions. Retosiban can be studied in research for preterm labour^[1][2][4]. IC50 & Target:IC50: 0.65 nM (Oxytocin)^[1] In Vitro:Retosiban (Compound GSK221149A) (0.1-10 μM) produces parallel rightward shifts of oxytocin-induced concentration-response curves in rat isolated myometrial strips^[4].
Retosiban (1 μM) alleviates the effect of stretch under high tension on myometrial contractility in tissues^[5]. In Vivo:Retosiban (Compound 22) has low to moderate intrinsic clearance in microsomes from three pre-clinical species (rat, dog, cynomolgus monkey)^[1].
Retosiban (1 nM-1 μM, i.v., single dose) produces a dose-dependent decrease in oxytocin-induced uterine contractions with an ID₅₀ = 0.27 mg/kg and IC₅₀ = 180 nM in anaesthetized and non-pregnant Sprague-Dawley female rats^[1].
Retosiban (Compound 74) (0.3-3 mg/kg, i.v., single dose) significantly reduced spontaneous uterine contractions in a dose-dependent manner in late-term pregnant rats^[3].
Retosiban (Compound GSK221149A) (0.1-1 mg/kg, i.v., single dose) results in a dose-dependent reduction in oxytocin-induced uterine contractions in anesthetized rats^[4].
Retosiban (5 mg/kg, p.o., once a day for 1 and 4 days) significantly blocks oxytoxin-induced uterine contractions by 72% in nulliparous female Sprague-Dawley rats^[4].