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. 1991 Feb;102(2):391–395. doi: 10.1111/j.1476-5381.1991.tb12184.x

Studies of three non-peptide cholecystokinin antagonists (devazepide, lorglumide and loxiglumide) in human isolated alimentary muscle and guinea-pig ileum.

M D'Amato 1, I F Stamford 1, A Bennett 1
PMCID: PMC1918051  PMID: 2015421

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.

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Selected References

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  1. Barthó L., Holzer P., Lembeck F., Lippe I. T., Setnikar I. Evaluation of a new and potent cholecystokinin antagonist on motor responses of the guinea-pig intestine. Br J Pharmacol. 1987 Apr;90(4):753–761. doi: 10.1111/j.1476-5381.1987.tb11229.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bennett A., Bloom S. R., Ch'ng J., Christofides N. D., Peacock L. E., Rennie J. A. Is vasoactive intestinal peptide an inhibitory transmitter in the circular but not the longitudinal muscle of guinea-pig colon? J Pharm Pharmacol. 1984 Nov;36(11):787–788. doi: 10.1111/j.2042-7158.1984.tb04877.x. [DOI] [PubMed] [Google Scholar]
  3. Bennett A., Misiewicz J. J., Waller S. L. Analysis of the motor effects of gastrin and pentagastrin on the human alimentary tract in vitro. Gut. 1967 Oct;8(5):470–474. doi: 10.1136/gut.8.5.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Black J. W., Leff P., Shankley N. P. Further analysis of anomalous pKB values for histamine H2-receptor antagonists on the mouse isolated stomach assay. Br J Pharmacol. 1985 Nov;86(3):581–587. doi: 10.1111/j.1476-5381.1985.tb08934.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang R. S., Lotti V. J. Biochemical and pharmacological characterization of an extremely potent and selective nonpeptide cholecystokinin antagonist. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4923–4926. doi: 10.1073/pnas.83.13.4923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cheng Y., Prusoff W. H. Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol. 1973 Dec 1;22(23):3099–3108. doi: 10.1016/0006-2952(73)90196-2. [DOI] [PubMed] [Google Scholar]
  7. Cross A. J., Slater P., Skan W. Characteristics of 125I-Bolton-Hunter labelled cholecystokinin binding in human brain. Neuropeptides. 1988 Feb-Mar;11(2):73–76. doi: 10.1016/0143-4179(88)90013-3. [DOI] [PubMed] [Google Scholar]
  8. D'Amato M., Stamford I. F., Bennett A. The effects of cholecystokinin octapeptide on human isolated alimentary muscle. Br J Pharmacol. 1990 May;100(1):126–130. doi: 10.1111/j.1476-5381.1990.tb12063.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Grider J. R., Makhlouf G. M. Regional and cellular heterogeneity of cholecystokinin receptors mediating muscle contraction in the gut. Gastroenterology. 1987 Jan;92(1):175–180. doi: 10.1016/0016-5085(87)90855-9. [DOI] [PubMed] [Google Scholar]
  10. Makovec F., Bani M., Cereda R., Chisté R., Pacini M. A., Revel L., Rovati L. A., Rovati L. C., Setnikar I. Pharmacological properties of lorglumide as a member of a new class of cholecystokinin antagonists. Arzneimittelforschung. 1987 Nov;37(11):1265–1268. [PubMed] [Google Scholar]
  11. SCHILD H. O. Drug antagonism and pAx. Pharmacol Rev. 1957 Jun;9(2):242–246. [PubMed] [Google Scholar]
  12. Setnikar I., Bani M., Cereda R., Chisté R., Makovec F., Pacini M. A., Revel L., Rovati L. C., Rovati L. A. Pharmacological characterisation of a new potent and specific nonpolypeptidic cholecystokinin antagonist. Arzneimittelforschung. 1987 Jun;37(6):703–707. [PubMed] [Google Scholar]

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