Gastric antisecretory effects of propantheline bromide and metiamide in rhesus monkeys

Abstract

The effects of propantheline bromide (PB) and metiamide (M), two dissimilar classes of gastric secretory inhibitors, were studied in chronic gastric fistula rhesus monkeys. Basal and stimulated gastric secretory studies were conducted in conscious monkeys. Multiple s.c. injections of either histamine or pentagastrin were given hourly for four consecutive hours. One hour after the injection of the stimulants a constant plateau of gastric secretion was reached, and the test compounds were then administered as a single i.v. bolus dose. Propantheline bromide at doses of 0.03--0.3 mg/kg inhibited basal and pentagastrin stimulated gastric secretion, but had no effect on histamine stimulation. Total acid output paralleled inhibition of volume of secretion, while there was little or no effect on acid concentration. Metiamide at the doses of 1--10 mg/kg inhibited basal, pentagastrin and histamine stimulated gastric secretion. Metiamide was equally effective in inhibiting the volume of secretion and acid concentration. The scope of the gastric secretory inhibition in the rhesus monkey achieved with these pharmacological agents is very similar to man. These results suggest that the rhesus monkey is an important animal model for predicting clinically useful gastric secretory inhibitors.