Methadone inhibition of vagally induced pancreatic and gastric secretions in rats: central and peripheral sites of action.

Pancreatic and gastric secretions after stimulation with acetylcholine, electrical vagal stimulation or 2-deoxyglucose injection were studied in anesthetized rats. The effects of methadone on these secretions were investigated. Maximal stimulation of pancreatic secretion by acetylcholine was not affected by methadone. Gastric acid stimulation by acetylcholine was only slightly decreased by methadone (30% or less). Electrical vagal stimulation of pancreatic and gastric secretions was progressively and dose-dependently decreased to a maximum of 50% by methadone. Maximal stimulation of pancreatic and gastric secretions by 2-deoxyglucose was completely suppressed by methadone with an ID50 of about 1 mg/kg and an ID100 of about 2.5 mg/kg for both secretions. It is concluded that methadone inhibits vagal stimulation of digestive secretions by acting both centrally and peripherally (probably by inhibiting the release of acetylcholine from vagal fibers). The central mechanism appears to be more important, since it occurs with lower doses and can produce complete suppression of secretion.