Pharmacological properties of lorglumide as a member of a new class of cholecystokinin antagonists.
Derivatives of 5-(dipentylamino)-5-oxo-pentanoic acid are a new class of non-peptide cholecystokinin (CCK) antagonists. The most potent compound, D,L-4-(3,4-dichlorobenzoylamino)-5-(dipentylamino)-5-oxo-pen tanoic acid (lorglumide, CR 1409), has a great affinity for the pancreatic CCK receptors and is a competitive, specific and potent CCK antagonist on the smooth muscles of the gall bladder and ileum of the guinea pig and on the CCK-induced amylase secretion of isolated pancreatic acini. In vivo lorglumide antagonizes the contraction of the gall bladder of the guinea pig and of the dog provoked by i.v. CCK-8 or ceruletide (caerulein). It antagonizes the satiety effect of CCK-8 in the rat and is protective against ceruletide-, taurocholate- and diet-induced pancreatitis. Lorglumide is therefore a useful pharmacological tool to study the functions of CCK. For its pharmacological properties, its relatively low toxicity and because it is active also after oral administration, lorglumide is a candidate for diagnostic or therapeutic use in man when an involvement of CCK is suspected.
Makovec
F
F
Rotta Research Laboratorium, Monza, Italy.
Bani
M
M
Cereda
R
R
Chisté
R
R
Pacini
M A
MA
Revel
L
L
Rovati
L A
LA
Rovati
L C
LC
Setnikar
I
I
D000818:Animals; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D004285:Dogs; D005704:Gallbladder / Q000187:drug effects; D005973:Glutamine / Q000031:analogs & derivatives*; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011949:Receptors, Cholecystokinin / Q000187:drug effects
D011949:Receptors, Cholecystokinin; D005973:Glutamine; D002766:Cholecystokinin; D011377:Proglumide; C048181:lorglumide