Effects of compound U74500A in animal models of gastric and duodenal ulceration.

Pretreatment with U74500A (up to 0.65 mg/100 g) failed to affect gastric lesions induced by 100% EtOH gavage in Sprague-Dawley rats. Topical application of U74500A did not reduce lesions induced by 40% EtOH in ex vivo gastric chamber preparations. However, pretreatment of rats with U74500A (0.65 g/100 g per os) reduced the incidence and severity of experimental duodenal ulcer induced by cysteamine HCl, and duodenal ulcer induced by cysteamine-HCl plus GABA. These results show U74500A to have powerful and specific antiduodenal ulcer actions. Pharmacologic analysis of organ-bath preparations of the small intestine show this compound to reduce intestinal contractility to applied cholinergic and serotonergic agonists. However, relaxations induced by electrical or nicotinic ganglionic stimulation were unaffected. U74500A itself caused concentration-dependent contractions.