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Pharmacological basis for the induction of gastric carcinoid tumours in the rat by loxtidine, an unsurmountable histamine H 2 ‐receptor blocking drug
Author(s) -
Brittain R.T.,
Jack D.,
Reeves J.J.,
Stables R.
Publication year - 1985
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1985.tb11083.x
Subject(s) - histamine , ranitidine , achlorhydria , histamine h2 receptor , antagonist , enterochromaffin like cell , chemistry , gastric acid , medicine , parietal cell , stomach , endocrinology , secretion , gastric mucosa , receptor , pharmacology , biology
1 The very late occurrence of gastric carcinoids in a life‐span carcinogenicity study with loxtidine in the rat might have resulted from continuous achlorhydria induced by this long‐acting unsurmountable histamine H 2 ‐antagonist. 2 The nature of the anti‐secretory activity of loxtidine was compared with that of ranitidine on histamine‐induced acid secretion in the perfused stomach preparation of the rat and in the rat isolated gastric mucosa preparation. 3 Ranitidine and loxtidine had qualitatively different inhibitory effects on acid secretion, ranitidine being a competitive antagonist of histamine even at high concentrations, whereas the effect of loxtidine on both preparations was unsurmountable at relatively low concentrations. 4 These results support the hypothesis that the late formation of gastric carcinoids in rats receiving loxtidine is a consequence of persistent achlorhydria caused by unsurmountable blockade of parietal cell H 2 ‐receptors.