Effect of Certain Histaminase Inhibitors on Gastric Secretion

Abstract

Dogs with Heidenhain pouches were used to study the effect of aminoguanidine (AG) and iproniazid (IPN) (1-isonicotinyl-2-isopropylhydrazine) (‘Marsilid’) on gastric secretion. AG and IPN given subcutaneously or orally were found to stimulate the basal secretion and to augment the gastric secretory response to a meal. In vitro studies have shown that AG is a diamino oxidase (DO) inhibitor and IPN is both a di- and monoamino oxidase (MO) inhibitor. IPN augments gastric secretion by its DO and not its MO inhibitor activity. Doses of IPN which cause evidences of mild toxicity depress gastric secretion. Evidence of the accumulative action of IPN on gastric secretion was obtained. Dogs vary considerably in their sensitivity to iproniazid. Since inflammation increases sensitivity to the gastric augmentory effects of both AG and IPN, and since man is 10 times more sensitive to histamine than the dog, it is suggested that the use of iproniazid in the treatment of active tuberculosis should augment gastric secretion, unless evidences of toxicity occur, and that the drug should be used cautiously in peptic ulcer patients. B1-pyrimidine, a DO inhibitor, given subcutaneously slightly augments the secretory response to a meal in a sensitive dog.