Description
Navacaprant (BTRX-335140) is a selective and orally active κ opioid receptor (KOR) antagonist, has antagonist activity for κOR, µOR and δOR with IC 50 values of 0.8 nM, 110 nM, and 6500 nM, respectively.Navacaprant endows with favorable in vitro ADMET and in vivo pharmacokinetic profiles and medication-like duration of action in rats. Navacaprant distributes well into the CNS and can be used for the research of neuropathyIn VitroNavacaprant (BTRX-335140) (0-10 µM; 4 h) shows selective antagonist activity towards Kappa Opioid Receptor. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Cell Viability AssayCell Line: OPRK1-BLA U2OS cells Concentration: 0-10 µM Incubation Time: 4 hours Result: Exibited antagonist activity to KOR, DOR and MOR with IC 50 values of 0.8, 110 and 6500 nM respectively, and showed selective antagonist activity to KOR.In VivoNavacaprant (BTRX-335140) (0.01-3 mg/kg; p.o. once) reduces U69,593- stimulated plasma prolactin secretion to levels of without U69,593 treatment. Navacaprant (BTRX-335140) (1 mg/kg; i.p. once) blocks U-50488-induced antinociception from hot water. 1.19 Pharmacokinetic Parameters of BTRX-335140 in rodents. Rats IV 1 mg/kg Mice IV 3 mg/kg Rats PO 5 mg/kg Mice PO 10 mg/kg CL (mL/min/kg) 105 66.5 t 1/2 (h) 1.81 1.91 6.19 2.57 AUC 0-t (h•ng/mL) 153 725 265 232 V ss (L/kg) 13.8 7.72 F (%) 30.2 12 MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Rat PRL model Dosage: 0.01, 0.03, 0.1, 0.3, 1 and 3 mg/kg Administration: Oral gavage; 0.01-3 mg/kg once Result: Effectively decreased the high level prolactin caused by U69,593 even at a dosage of 0.1 mg/kg. Animal Model: Adult male ICR mice with tail dipped into 50°C hot water Dosage: 1 mg/kg Administration: Intraperitoneal injection; 1 mg/kg once Result: Blocked the U-50488-induced antinociception at 1 h but not at 24 h pretreatment time and showed a medication-like duration of action in blocking the KOR.Form:SolidIC50& Target:κ Opioid Receptor/KOR 0.8 nM (IC 50 ) µ Opioid Receptor/MOR 110 nM (IC 50 ) δ Opioid Receptor/DOR 6500 nM (IC 50 )