The effect of drugs interfering with biogenic amines metabolism on gastric secretion and reserpine-ulcers development in rats.

The effect of drugs interfering with endogenous catecholamines metabolism on gastric secretion and gastric ulcers development 4 hr following reserpine administration was investigated in rats with chronic gastric fistulas. Drugs inhibiting catecholamine synthesis: alpha-methyl-p-tyrosine (alpha-MT) and sodium diethyldithiocarbamate (DDC) decreased substantially the reserpine-induced gastric acid and pepsin secretion, but only alpha-MT diminished the development of gastric ulcers. Pretreatment with nialamide (NLD) elicited in reserpinized rats a marked inhibition both of gastric secretion and of gastric ulcers development. Dopamine (DA), noradrenaline (NA) and adrenaline (A) decreased the secretion of hydrochloric acid but did not change the intensity of gastric ulcers caused by reserpine. Desipramine strongly inhibited reserpine-induced gastric acid secretion. Reserpine depleted DA, NA and 5-HT stores in the brain and decreased DA and 5-HT levels in the wall of the stomach in which the NA levels were increased. The changes in biogenic amines content induced by drugs in reserpinized rats did not correlate with their influence on gastric secretion and on the development of mucosal ulcers. The inhibitory effect of all of the drugs examined on gastric acid and pepsin secretion in reserpinized rats was accompanied by the inhibition of gastric ulcers formation following NLD and alpha-MT administration only, indicating that ulcer generation following reserpine depends more on changes in mucosal barrier resistance than on gastric acid secretion.