An acid-independent antiulcer effect of M1 antimuscarinics in the rat.

In the rat, the antiulcer potencies of the M1 antimuscarinics telenzepine and pirenzepine, the H2 receptor blocker cimetidine, and the H+/K+-ATPase inhibitor omeprazole were compared with their antisecretory potencies. On a molar basis and with regard to inhibition of cysteamine-induced acid secretion, telenzepine ranked first, followed by omeprazole, cimetidine, and pirenzepine; cysteamine-induced duodenal ulcers were best inhibited by telenzepine, with pirenzepine, omeprazole and cimetidine ranking 2nd, 3rd and 4th. Up to the highest dose tested, cimetidine and omeprazole caused inhibition by 26 and 37%, respectively. While, with the antimuscarinics, lesion inhibition runs parallel with inhibition of acid secretion, the H2 receptor blocker and the H+/K+-ATPase inhibitor markedly impair acid secretion, but do not or merely negligibly inhibit cysteamine-induced formation of duodenal ulcers. This suggests that in this animal model the antiulcer effect cannot be attributed exclusively to the antisecretory action.