L-365260 hemihydrate is a selective, orally active non-peptide gastrin and brain cholecystokinin receptor (CCK-B) antagonist, demonstrating competitive interaction with guinea pig stomach gastrin and brain CCK receptors and exhibiting inhibition constants (Kis) of 1.9 nM and 2.0 nM, respectively.

L-365260 hemihydrate demonstrates a high affinity for the CCK-B receptors in the brains of rats, mice, and humans, while showing a reduced affinity for both gastrin and CCK-B (IC 50 =20-40 nM) receptors in dog tissues [1]. At a concentration of 1 μM, L-365260 hemihydrate significantly diminishes the depolarization induced by CCK8S and CCK4 in distinct neurons [2].

L-365260 hemihydrate, administered orally (0.1-30 mg/kg), inhibits gastrin-induced acid secretion in mice (ED50=0.03 mg/kg), rats (ED50=0.9 mg/kg), and guinea pigs (ED50=5.1 mg/kg) [1]. When given subcutaneously (0.01-10 mg/kg), it potentiates analgesic effects of a submaximal dose of Morphine (4 mg/kg) in rats, and a dosage of 0.2 mg/kg administered twice daily for five days markedly extends Morphine analgesia duration in the same species [3]. These effects were assessed using male Sprague-Dawley rats weighing 300-350 g and pre-injected with Morphine [3], with the compound administered subcutaneously 10 minutes before an intraperitoneal Morphine injection of 4 mg/kg, showing significant enhancement in Morphine-induced analgesia at dosages ranging from 0.01 to 10.0 mg/kg.