Metoclopramide enhances bethanechol-induced pancreatic exocrine secretion of the dog

The effects of metoclopramide on pancreatic exocrine secretion were investigated in the pentobarbitone-anaesthetized dog. All drugs were injected into the femoral vein. Metoclopramide (10-1000 micrograms/kg) did not change the resting rate of pancreatic secretion. Pancreatic secretion, induced by bethanechol (3 micrograms/kg), was dose-dependently enhanced by simultaneous injections of metoclopramide (10 and 30 micrograms/kg), but the protein and bicarbonate concentrations of the pancreatic juice were not affected. Secretions induced by secretin (0.1 units/kg) and dopamine (3 micrograms/kg) were not modified by metoclopramide at up to 30 micrograms/kg. A larger dose of metoclopramide (1000 micrograms/kg) suppressed dopamine-induced secretion to a lesser extent than the same dose of sulpiride. From these results, it is concluded that metoclopramide enhances secretory responses to cholinergic stimulations by peripherally sensitizing the muscarinic receptor-mediated exocrine process and this drug is a weaker antagonist of the dopamine D2 receptors than sulpiride.