OT-R antagonist 1 is a new potent and selective nonpeptide low molecular weight OT-R antagonist. OT-R antagonist 1 inhibits oxytocin-evoked intracellular Ca2+ mobilization (IC50 = 8 nM). IC50 value: 8 nM Target: oxytocin receptor in vitro: OT-R antagonist 1 inhibitis IP3-Synthesis, rat OT-R (IC50=0.03 uM). [4] OT-R antagonist 1 inhibits phosphodiesterase IV with IC50 = 6.1 μM, a value about 300-fold higher than the affinity for OT-R. OT-R antagonist 1 shows a very clean selectivity profile with specific interaction with OT-R. OT-R antagonist 1 competitively inhibits binding of [3H]oxytocin and the peptide antagonist 125I-ornithine vasotocin analog to human and rat oxytocin receptor expressed in human embryonic kidney 293-EBNA or Chinese hamster ovary cells with nanomolar potency. Selectivity against vasopressin receptor subtypes is >6-fold for V1a and >350-fold for V2 and V1b. in vivo: Oxytocininduced contraction of isolated rat uterine strips is blocked by OT-R antagonist 1 (pA2 = 7.82). In anesthetized nonpregnant rats, single administration of OT-R antagonist 1 by i.v. or oral routes causes dose-dependent inhibition of contractions elicited by repeated injections of oxytocin with ED50 = 3.5 mg/kg i.v. and 89 mg/kg p.o., respectively. OT-R antagonist 1 significantly inhibits spontaneous uterine contractions in pregnant rats near term when administered intravenously or orally.

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