Loxiglumide is a cholecystokinin (CCK) receptor antagonist that inhibits CCK-8 binding to central and peripheral CCK receptors with Ki values of 9.1 and 0.33 μM, respectively.1 It inhibits CCK-8-induced release of acetylcholine from isolated guinea pig gallbladder (IC50 = 10 nM).2 Loxiglumide (50 μM) reduces the invasion of PANC-1 and MiaPaCa-2 human pancreatic cancer cells by 83.1 and 82.9%, respectively, in vitro.3 Loxiglumide (10-5,000 μM) reduces DNA synthesis in PC-TI and PC-YY human pancreatic cancer cells in a concentration-dependent manner (IC50s = 160 and 74 μM, respectively).4 It reduces the tumor growth rate by 37.5 and 38%, respectively, in PC-TI and PC-YY mouse xenograft models when administered at a dose of 250 mg/kg. Loxiglumide is toxic to mice with LD50 values ranging from 440 to 500 mg/kg dependent on the route of administration. In a rat model of acute pancreatitis, loxiglumide (50 mg/kg, s.c.) reduces serum concentrations of CCK, amylase, and lipase by greater than 60%, as well as tissue hemorrhaging and acinar cell necrosis.5
1.Setnikar, I., Bani, M., Cereda, R., et al.Pharmacological characterisation of a new potent and specific nonpolypeptidic cholecystokinin antagonistArzneimittelforschung37(6)703-707(1987) 2.Rakovska, A., Sgaragli, G., Mantovani, P., et al.Effect of loxiglumide (CR 1505) on CCK-induced contractions and 3H-acetylcholine release from guinea-pig gallbladderNeuropeptides25(5)271-276(1993) 3.Hirata, M., Itoh, M., Tsuchida, A., et al.Cholecystokinin receptor antagonist, loxiglumide, inhibits invasiveness of human pancreatic cancer cell linesFEBS. Lett.383(3)241-244(1996) 4.Nio, Y., Tsubono, M., Morimoto, H., et al.Loxiglumide (CR 1 505), a cholecystokinin antagonist, specifically inhibits the growth of human pancreatic cancer lines xenografted into nude miceCancer72(12)3599-3606(1993) 5.Tani, S., Itoh, H., Koide, M., et al.Involvement of endogenous cholecystokinin in the development of acute pancreatitis induced by closed duodenal loopPancreas8(1)109-115(1993)