Effects of tandamine and pirandamine, selective blockers of biogenic amine uptake mechanisms, on gastric acid secretion and ulcer formation in the rat

Abstract

Tandamine and pirandamine and various structurally-related compounds, which were known to inhibit the norepinephrine and/or serotonin uptake mechanisms, lack central anticholinergic activity and differ chemically from the known tricyclic antidepressant drugs, were examined for their effects on gastric acid secretion and ulcer formation in the rat. Tandamine and its structurally-related compounds, but not pirandamine or its structurally-related compound, given intraperitoneally, inhibited gastric acid secretion and were similar in activity to imipramine. Like imipramine, tandamine was effective when given perorally. None of the compounds examined, administered intraperitoneally, were effective in reducing the ulcer formation in 19 h pylorus-ligated animals, while imipramine was effective. Tandamine, like imipramine, inhibited ulcer formation in 10 h pylorus-ligated animals and in 19 h pylorus-ligated animals when given in divided doses. Tandamine and its structurally-related compounds, but not pirandamine or its structurally-related compound, given subcutaneously, prevented reserpine-induced gastric ulceration; imipramine was also effective. Tandamine and imipramine, administered intraperitoneally, prevented cold-restraint gastric ulceration. The compounds which block the norepinephrine, or in addition the serotonin, uptake mecahnism, but not those which block only the serotonin uptake mechanism, inhibited the gastric acid secretion and reserpine-induced ulceration. Thus, these latter activities appear to be correlated with the inhibition of the norepinephrine, rather than serotonin uptake mechanism.