[Inhibitory effect of CR 1409 (cholecystokinin antagonist) on pancreatic exocrine secretion in rats].
New cholecystokinin (CCK) receptor antagonist, CR 1409 (lorglumide), was evaluated for anti-CCK activity on pancreatic exocrine secretion in anesthetized rats in vivo, compared with proglumide. Both CR 1409 in a dose range of 0.04-25 mg/kg-hr and proglumide in a dose range of 30-600 mg/kg-hr given intravenously, showed significant inhibitory effect on pancreatic secretion in terms of juice volume and amylase output stimulated by intravenous CCK-8 (0.06 micrograms/kg-hr), in a dose-related manner. CR 1409 is about 1000 times more potent than proglumide, based on ED 50. Furthermore, intravenous administration of either CR 1409 (5 mg/kg-hr) or proglumide (600 mg/kg-hr) resulted in significant suppression on pancreatic secretion stimulated by intraduodenal casein in a dose of 400 mg/hr. Thus, very potent CCK receptor antagonist, CR 1409, inhibited pancreatic exocrine secretion stimulated by not only exogenous CCK, but also intraduodenal casein in rats.
Shiratori
K
K
Watanabe
S
S
Shimizu
K
K
Moriyoshi
Y
Y
Chang
J H
JH
Takeuchi
T
T
D000681:Amylases / Q000378:metabolism; D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D005973:Glutamine / Q000031:analogs & derivatives*; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism*; D010189:Pancreatic Juice / Q000378:metabolism; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000037:antagonists & inhibitors
D005973:Glutamine; D002766:Cholecystokinin; D000681:Amylases; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide