Loxiglumide

Loxiglumide is a cholecystokinin (CCK) receptor antagonist that inhibits CCK-8 binding to central and peripheral CCK receptors with K_i 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

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1. Setnikar, I., Bani, M., Cereda, R., et al. Pharmacological characterisation of a new potent and specific nonpolypeptidic cholecystokinin antagonist. Arzneimittelforschung 37(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 gallbladder. Neuropeptides 25(5), 271-276 (1993).

3. Hirata, M., Itoh, M., Tsuchida, A., et al. Cholecystokinin receptor antagonist, loxiglumide, inhibits invasiveness of human pancreatic cancer cell lines. FEBS. 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 mice. Cancer 72(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 loop. Pancreas 8(1), 109-115 (1993).