SR 146131

SR 146131 is a potent, orally available, and selective nonpeptide (cholecystokinin 1) receptor agonist. IC50 & Target: Cholecystokinin 1 receptor^[1] In Vitro: SR 146131 inhibits in the binding of [¹²⁵I]-BH-CCK-8S to CCK1sites on 3T3-hCCK1 cell membranes with an IC₅₀ value of 0.56 ± 0.10 nM. At much higher concentrations, SR 146131 also inhibits the binding of radiolabeled CCK to CCK2sites in CHO-hCCK2 membranes with an IC₅₀ of 162 ± 27 nM. SR 146131 is a potent CCK1 agonist on several intracellular events linked to CCK1 receptor activation in various cell types: on [Ca²⁺]i release and IP1 formation, SR 146131 appears as a full CCK1 receptor agonist in the 3T3-hCCK1 cells, but a partial CCK1receptor agonist on MAPK activation and early gene expression in this cell line. SR 146131 also acts as a partial agonist in the two neuroblastoma cell lines^[1]. In Vivo: SR 146131 completely inhibits gastric and gallbladder emptying in mice (ED₅₀ of 66 and 2.7 μg/kg p.o., respectively). SR 146131 dose dependently reduces food intake in fasted rats (from 0.1 mg/kg p.o.), in nonfasted rats in which food intake has been highly stimulated by the administration of neuropeptide Y (1–36) (from 0.3 mg/kg p.o.), in fasted gerbils (from 0.1 mg/kg p.o.), and in marmosets maintained on a restricted diet (from 3 mg/kg p.o.). SR 146131 (10 mg/kg p.o.) also increases the number of Fos-positive cells in the hypothalamic paraventricular nucleus of rats. Locomotor activity of mice is reduced by orally administered SR 146131 (from 0.3 mg/kg p.o.)^[1].