STUDIES OF 3 NONPEPTIDE CHOLECYSTOKININ ANTAGONISTS (DEVAZEPIDE, LORGLUMIDE AND LOXIGLUMIDE) IN HUMAN ISOLATED ALIMENTARY MUSCLE AND GUINEA-PIG ILEUM

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 pK(B), +/- 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 pK(B) 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 pK(B) values obtained from classical competition experiments were: devazepide, 10.09; 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.