Antispasmodic activity on the gallbladder of the mouse of CR 1409 (lorglumide) a potent antagonist of peripheral CCK.
Cholecystokinin (CCK) is a hormonal regulator of the motility of the gallbladder. CCK-8, i.e. the biologically active C-terminal octapeptide of the hormone, elicits contraction and emptying of the gallbladder. Endogenous CCK released by egg yolk or fatty acids in the duodenum gives the same results. CR 1409 (lorglumide), a glutaramic acid derivative with peripheric competitive CCK-antagonistic activity, was evaluated in comparison with proglumide (the model CCK-receptor antagonist) and other conventional antispasmodic drugs, for their ability to inhibit the emptying of the gallbladder induced in mice by CCK-8 or by lyophylized egg yolk. CR 1409 (1-10 mg/kg) prevented dose-dependently the emptying of the gallbladder in both experimental models; proglumide exhibited a comparable activity at much higher doses (200-800 mg/kg). On the contrary the anticholinergic drug atropine, the calcium-antagonist nifedipine, and the phosphodiesterase inhibitor papaverine were almost ineffective. The present data support the hypothesis that the effects of CCK on gallbladder motility are mediated by a CCK-dependent specific mechanism.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005704:Gallbladder / Q000187:drug effects*; D005973:Glutamine / Q000031:analogs & derivatives*; D051379:Mice; D008815:Mice, Inbred Strains; D009543:Nifedipine / Q000494:pharmacology; D010208:Papaverine / Q000494:pharmacology; D010276:Parasympatholytics; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology
D010276:Parasympatholytics; D005973:Glutamine; D001285:Atropine; D002766:Cholecystokinin; D010208:Papaverine; D011377:Proglumide; D009543:Nifedipine; C048181:lorglumide