Antagonism of Stress‐Induced Gastric Motor Alteration and Plasma Cortisol Release by Fedotozine (JO 1196) in Dogs

Abstract

The effects of fedotozine (a new dimethyl propylamine derivative) on gastric motor inhibition and plasma cortisol increase induced by acoustic stress were investigated in fasted dogs fitted with strain‐gauge transducers on the antrum and proximal jejunum and an implanted jugular catheter. Stress was induced by 1 hour of music (≤90 dB) played through earphones. Starting 40 to 50 minutes after the last migrating motor complex (MMC), acoustic stress delayed by 131% the next gastric MMC, whereas intestinal motility was unaffected. Plasma cortisol increased (p < 0.05) by 516%, 30 minutes after the beginning of noise. The inhibition of gastric MMC as well as the hypercortisolemia induced by acoustic stress were reduced in a dose‐related manner or abolished by previous oral administration of fedotozine (0.1–1 mg/kg) but not by intravenous injection (0.1–0.5 mg/kg). The effect of fedotozine was abolished after previous intravenous treatment with MR 2266 (0.1 mg/kg). Only the motor effects were suppressed by naloxone (0.1 mg/kg i.v.), which induced a significant (p < 0.05) increase in plasma level. Bilateral truncal vagotomy, which suppressed the effects of acoustic stress on gastric motility but not on plasma cortisol, suppressed the antagonistic influence of fedotozine on hypercortisolemia. We conclude that fedotozine administered orally reduces both stress‐induced gastric motor alterations and hypercortisolemia, probably by acting directly on K receptors present in the intestinal wall that activate vagal afferent fibers interacting, at the central nervous system level, with factors responsible for the gastric and endocrine alterations induced by stress.