Aticaprant (CERC-501) is a potent and centrally-penetrant antagonist of the kappa-opioid receptor (Ki: 0.807 nM).[2]

κ opioid:0.807 nM (Ki)

Aticaprant(CERC-501) binds with a high affinity to the human kappa opioid receptor with a 30-fold higher affinity over the human mu-opioid receptor and a 190-fold higher affinity over the human delta-opioid receptor. Aticaprant(CERC-501) shows no appreciable affinity for several non-opioid cell surface G-protein-coupled receptor targets [1].

METHODS: Mice were given Aticaprant(CERC-501) (0.1 to 3 mg/kg, intraperitoneal injection) 30 minutes before the alcohol deprivation effect (ADE) test and naltrexone (0.3 or 1 mg/kg, intraperitoneal injection) 10 minutes before the test to observe the effect of aticaprant on the ADE effect.
RESULTS 0.3 mg/kg of Aticaprant(CERC-501) and 1 mg/kg of naltrexone reduced the ADE alcohol intake of mice at 4 hours. [1]

Three male cannulated rats are administered a single 1 mg/kg intravenous (IV) and 10 mg/kg oral (PO) dose of Aticaprant to determine the pharmacokinetic parameters. Plasma samples are collected at 0.08 (IV only), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 h post-dose and analyzed by liquid chromatography coupled to tandem mass spectral detection to determine the concentrations of Aticaprant (CERC-501). Male mice are administered a single 10 mg/kg PO dose of Aticaprant to determine the pharmacokinetic parameters. Plasma samples are collected at 0.5, 1, 2, 4, 8, and 24 h post-dose and analyzed by LCMS/MS to determine the concentrations of Aticaprant. The plasma and brain binding of Aticaprant is determined by equilibrium dialysis at 1 μM [1].