Pharmacological basis for the induction of gastric carcinoid tumours in the rat by loxtidine, an unsurmountable histamine H2‐receptor blocking drug

Abstract

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 H₂-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 H₂-receptors.