Although ONO-7300243 showed only modest in vitro activity (IC50 = 0.16 μM), it showed much stronger effects in vivo (88% inhibition at 10 mg/kg i.d., 62% inhibition at 3 mg/kg i.d.). ONO-7300243 showed good membrane permeability and good metabolic stability against rat liver microsomes.
In vivo
ONO-7300243 inhibited the LPA-induced IUP(intraurethral pressure) increase in a dose-dependent manner (ID50 = 11.6 mg/kg p.o.) up to 1 h after dosing. Significant effects were observed at 10 and 30 mg/kg (p<0.05 vs vehicle). ONO-7300243 (30 mg/kg, p.o.) led to a significant decrease in the IUP in conscious rats without LPA stimulation compared with the vehicle without affecting the mean blood pressure (MBP). In a a rat pharmacokinetic study, ONO-7300243 showed a rapid clearance (CLtot = 15.9 mL/min/kg at 3 mg/kg i.v.) and a short half-life (0.3 h).
