title: The effect of a novel CCK-antagonist (lorglumide) on human and guinea pig gallbladder strips: a tensiometric study.
abstract: The effect of a novel CCK-antagonist (lorglumide, CR 1409) was evaluated by "in vitro" tensiometric studies on 16 human (gallstone patients) and 12 guinea pig gallbladder smooth muscle strips. In the animal experiments, increasing doses of lorglumide (0.2-6.5 uM) caused a rightward shift of the dose-response curves of CCK-OP, with an increase of the ED50 from 8.2 nM +/- 1.62 SEM, n = 12; to 100 nM +/- 12, n = 4) without affecting the maximal effect (Emax). Schild plot gave an affinity constant of 7.19. In human gallbladders, the effect of lorglumide was also present (ED50 increased from 47 nM +/- 8 SEM, n = 16; to 300 nM +/- 10 SEM, n = 4) coexisting with a large inter-sample variation for CCK-OP ED50s and maximal contractions, most likely due to the histological changes of the wall in chronic cholecystitis. The affinity constant was similar to that found in animal experiments. We confirm the studies previously reported in animals on the existence of a competitive antagonism of lorglumide on CCK gallbladder receptors. Moreover, our results on gallbladders from gallstone patients show that lorglumide is a highly effective antagonist of CCK-induced contractions despite the presence of chronic cholecystitis. Our study might help for a better comprehension of the role of these new anti-CCK drugs in the treatment of biliary pain.
authors: Institute of Clinica Medica 1st., University of Bari.
authors: P
authors: P
authors: Portincasa
authors: R
authors: R
authors: Brandonisio
authors: A
authors: A
authors: Di Ciaula
authors: V
authors: V
authors: Maggi
authors: M
authors: M
authors: Chiloiro
authors: G
authors: G
authors: Palasciano
mesh_terms: D000328:Adult; D000368:Aged; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005704:Gallbladder / Q000187:drug effects*; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D011377:Proglumide / Q000031:analogs & derivatives* / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000187:drug effects; D012844:Sincalide / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013045:Species Specificity
chemical_list: D011949:Receptors, Cholecystokinin; D011377:Proglumide; C048181:lorglumide; D012844:Sincalide