L-368,899 HYDROCHLORIDE

IC50: 8.9 nM (rat uterus oxytocin receptor), 26 nM (human uterus oxytocin receptor)

L-368,899 hydrochloride is a potent, orally bioavailable, non-peptide oxytocin receptor antagonist, with IC ₅₀ s of 8.9 nM and 26 nM for rat uterus and human uterus oxytocin receptor, respectively. L-368,899 is less active on VP receptor in human liver and kidney, rat liver and kidney (IC ₅₀ , 510 nM, 960 nM, 890 nM, 2400 nM, respectively).

L-368,899 exhibits similar pharmacokinetics in rats and dogs. After a single iv. injection, L-368,899 had a t _1/2 of 2 hr in both species. Additionally, L-368,899 has a plasma clearance between 23 and 36 ml/min/kg in rats or dogs. L-368,899 exhibits V _dss values of 2.0 and 2.6 liters/kg and 3.4 to 4.9 liters/kg for dogs, respectively. L-368,899 is orally available. In the rat, at the 5 mg/kg dose, the oral bioavailabilities are 14% and 18% for female and male rats, respectively. Additionally, the oral bioavailabilities are 17% and 41% for female and male rats, respectively at the dosage of 25 mg/kg.