Pharmacological studies of loperamide, an anti-diarrheal agent. I. Effects on diarrhea induced by castor oil and prostaglandin E1.

Abstract

Effects of loperamide on diarrhea induced by castor oil and prostaglandin E1 were investigated in rats and mice and compared with those of narcotic analgesics, atropine, mecamylamine and local anesthetics. Loperamide markedly suppressed the appearance of diarrhea induced by oral administration of castor oil in rats and the ED50 values for 1 and 2 h protection was 0.082 and 0.42 mg/kg orally, respectively. Loperamide markedly suppressed the appearance of diarrhea induced by i.v. administration of prostaglandin E1 and the ED50 value for 2 h protection was 0.24 mg/kg orally in rats. The loperamide ID120 min value [dose producing a 20% or more inhibition of the charcoal transport in the small intestine for 120 min] was 0.8 mg/kg orally in mice and this activity was 9.2 times more potent than that of morphine. The analgesic ED50 value (Haffner''s method) and LD50 value of loperamide was 149 and 249 mg/kg orally, respectively. Apparently loperamide has a potent anti-diarrheal activity and specificity to the gastrointestinal tract and inhibits the effect of prostaglandin E1 and ricinoleic acid on the intestinal tract in rats.