3--AMINOETHYL-1,2,4-TRIAZOLE, A POTENT STIMULANT OF GASTRIC SECRETION

¹ The Lilly Research Laboratories, Indianapolis, Indiana

In rats histamine and 3--aminoethyl-1,2,4-triazole at dose levels of 10 to 40 mg/kg administered orally 1 hour before ligation of the pyloric-duodenal junction stimulated the secretion of gastric HCl without significantly altering the volume of the gastric secretion. Given subcutaneously, neither histamine nor the triazole stimulated gastric HCl or volume under comparable conditions. When the compounds were administered orally immediately after the ligation of the pylorus, the gastric HCl was increased by 20 to 40 mg/kg of histamine and by 40 mg/kg of the triazole, but it was not affected by subcutaneous administration of similar doses.

In dogs the triazole was one of the most powerful gastric stimulators known. Subcutaneously, it had about 60% of the potency of histamine on gastric stimulation, whereas orally it was approximately 20 times as potent as histamine. A dose of 25 µg/kg of the triazole invariably stimulated the gastric secretion of HCl of all dogs with innervated or denervated gastric pouches. A hyperbolic curve illustrating the dose-response relationship between orally administered triazole and gastric HCl output could be obtained for doses between 25 and 3000 µg/kg.

Histamine, on the contrary, was relatively ineffective orally at pharmacological doses; 0.5 mg/kg of the base was required to elicit a response in all dogs studied. In addition a dose-response relationship between orally administered histamine and gastric production of HCl was not obtainable in most of the dogs tested.

Large doses of the triazole given orally caused histamine-like reactions, some of which were antagonized by pyrrobutamine, an anti-histaminic.

The triazole was about 72 to 73% as potent as histamine in its effect on the motility of the isolated guinea-pig ileum and on the blood pressure of the anesthetized cat. The pharmacological and physiological significance of these findings has been discussed.