title: Studies of three non-peptide cholecystokinin antagonists (devazepide, lorglumide and loxiglumide) in human isolated alimentary muscle and guinea-pig ileum.
abstract: 1. Three recently described non-peptide cholecystokinin (CCK) antagonists (devazepide, lorglumide, loxiglumide) have been studied for their antagonism of the contraction to cholecystokinin-octapeptide (CCK-OP) in human alimentary muscle and guinea-pig intestine. 2. Each antagonist caused a concentration-dependent inhibition of the contraction induced by CCK-OP, regardless of regional and species differences. 3. The potencies of each drug, estimated by use of an adaptation of the Cheng & Prusoff equation, were similar in the different regions of human alimentary tract (weighted mean apparent pKB, +/- s.e. mean: devazepide, 5.76 +/- 0.08, n = 20; lorglumide, 5.82 +/- 0.04, n = 25; loxiglumide, 5.87 +/- 0.07, n = 24). 4. In contrast, the potencies differed markedly in the guinea-pig ileum. Apparent pKB values obtained by the same method as with human tissues were, mean +/- s.e.mean: devazepide, 10.61 +/- 0.61; lorglumide, 7.43 +/- 0.20; loxiglumide, 6.67 +/- 0.12. pKB values obtained from classical competition experiments were: devazepide, 10.09 +/- 0.09; lorglumide 7.70 +/- 0.12; loxiglumide 6.08 +/- 0.22. 5. The CCK receptors in human gut muscle from different regions seem to be similar, but there appear to be species differences.
authors.affiliation: Department of Surgery, King's College School of Medicine and Dentistry, Rayne Institute, London.
authors.forename: M
authors.initials: M
authors.lastname: D'Amato
authors.forename: I F
authors.initials: IF
authors.lastname: Stamford
authors.forename: A
authors.initials: A
authors.lastname: Bennett
mesh_terms: D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors*; D020109:Devazepide; D004064:Digestive System / Q000187:drug effects; D004068:Digestive System Physiological Phenomena; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D011949:Receptors, Cholecystokinin / Q000187:drug effects / Q000502:physiology; D012844:Sincalide / Q000494:pharmacology
chemical_list: D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; C053737:loxiglumide; D002766:Cholecystokinin; D011377:Proglumide; D020109:Devazepide; C048181:lorglumide; D012844:Sincalide