L-365260

L-365260 is an orally active and selective antagonist of non-peptide gastrin and brain cholecystokinin receptor (CCK-B), with K_is of 1.9 nM and 2.0 nM, respectively. L-365260 interacts in a stereoselective and competitive manner with guinea pig stomach gastrin and brain CCK receptors. L-365260 can enhance Morphine analgesia and prevents Morphine tolerance^[1][2][3]. IC50 & Target:Ki: 1.9 nM (gastrin); 2.0 nM (CCK-B)^[1]. In Vitro:L-365260 (1 μM) strongly attenuates the CCK8S- and CCK4-mediated depolarization in a different neuron^[2].
L-365260 exhibits a similar high affinity for brain CCK-B receptors of rats, mice and man, and a lower affinity for gastrin and brain CCK-B (IC₅₀=20-40 nM) receptors in dog tissues^[1]. In Vivo:L-365260 (0.01-10 mg/kg; s.c.) enhances analgesia induced by a submaximal dose of Morphine (4 mg/kg) in rats^[3].
L-365260 (0.2 mg/kg; s.c. twice daily for 5 days) significantly prolongs the duration of Morphine analgesia in rats^[3].
L-365260 (0.1-30 mg/kg; p.o.) antagonizes gastrin-stimulated acid secretion in mice (ED₅₀=0.03 mg/kg), rats (ED₅₀=0.9 mg/kg) and guinea pigs (ED₅₀=5.1 mg/kg)^[1].