Effects of prolonged treatment of pirenzepine 2HCl on gastric secretion and plasma gastrin levels in rats.

Gastric secretory functions and plasma gastrin levels in rats after the prolonged treatment of pirenzepine 2HCl were evaluated. Pirenzepine 2HCl at 100 mg/kg was given p.o. twice daily for 4 weeks. Control animals were given saline alone. The test agent potently inhibited gastric secretion in pylorus-ligated rats and fistula rats stimulated with pentagastrin and histamine before and after cessation of 4 weeks' treatment. At 1 day after the treatment, the acid output slightly decreased in pylorus-ligated rats and significantly decreased in fistula rats stimulated with secretagogues. At 3 days, the acid output was slightly increased in pylorus-ligated rats and significantly increased in fistula rats stimulated with pentagastrin but was unchanged in the case of histamine stimulation. At 10 days, the gastric secretion in pylorus-ligated rats tended to increase but the acid output in fistula rats was not affected. Pirenzepine 2HCl increased the plasma gastrin levels in normal rats and at 1 day after the treatment, but had no effects at 3 and 10 days. Propantheline Br showed much the same results as seen with pirenzepine 2HCl. Cessation of prolonged treatment with pirenzepine 2HCl appears to increase only slightly and transiently the sensitivity of gastric secretory cells.