Loperamide antagonism of castor oil-induced diarrhea in rats: a quantitative study.

The time-course of castor oil-induced diarrhea in fasted rats was quantified by weighing stools every 15 minutes for 8 hours after the challenge and then after 24 hours. Diarrhea began within 1 hour as a series of rapidly occurring evacuations over 20 to 40 minutes. The mean weight of these stools was 5.7 g; later irregular evacuations increased the weight to 9.4 g at 8 hours. The area of individual time-weight diagrams had a median value of 432 units. Pretreatment with 0.16 mg/kg of loperamide, a new antidiarrheal drug, significantly decreased the area of similarly obtained diagrams; 0.31 mg/kg caused a 50% reduction. This antagonism by loperamide of castor oil-induced diarrhea may involve reduction in the severity of inflammatory changes in the intestinal wall.