Effect of Z-203, a CCK-A receptor antagonist, on rat pancreatic exocrine secretion and experimental acute pancreatitis models

• Published in: Japanese Journal of Pharmacology Vol. 79; no. suppl.1; p. 209
• Main Authors: Yoshinaga, Koji, Washizuka, Masataka, Higashino, Raita, Fukuda, Youichi, Fukuta, Yoshihisa, Takei, Mineo, Furuichi, Hiroyasu, Tanaka, Yoshiaki
• Format: Journal Article
• Language: English
• Published: The Japanese Pharmacological Society 1999
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)34849-8

The effects of intravenous administration of Z-203 [sodium(S)-1-(2-fluorophenyl)-2,3-dihydro-3-[(3-isoquinolylcarbonyl)amino]-6-methoxy-2-oxo-1H-indole-3-propanoate], on rat pancreatic exocrine secretion and experimental acute pancreatitis models were studied. 1. Z-203 suppressed the casein-stimulated increases of pancreatic juice volume and outputs of amylase and protein in rats. 2. Z-203 prevented the caerulein-induced increase of serum amylase activity in mice (ED_50 =0.053 mg/kg, i.v.) and rats (ED_50 =0.055 mg/kg, i.v.). 3. Z-203 prevented the pancreatic duct ligation-induced increase of serum amylase activity in a dose-dependent manner, with an ED_50 value of 0.023 mg/kg. Furthermore, Z-203 was effective against the pancreatitis induced by this model when administered 1 h after pancreatic duct ligation. These results indicate that Z-203 has a potent inhibitory action on pancreatic exocrine secretion and a preventive effect in models of acute pancreatitis. Therefore, Z-203 will be a useful drug for treatment of human acute pancreatitis.