In vivo antimotility and antidiarrheal activity of lidamidine hydrochloride (WHR-1142A), a novel antidiarrheal agent. Comparison with diphenoxylate and loperamide.

1-(2,6-Dimethylphenyl)-3-methyl-amidinourea hydrochloride (WHR-1142A, lidamidine hydrochloride) was shown to have potent antimotility, antidiarrheal and intestinal antisecretory activity in mice, rats and dogs. Antimotility activity was demonstrated in charcoal intestinal motility, gastric emptying and gastric and intestinal intraluminal pressure studies. Antidiarrheal activity was evaluated in castor oil-, prostaglandin E2-, carbachol-, and serotonin-induced diarrhea. Intestinal secretion induced by cholera toxin was inhibited by WHR-1142A. In general, WHR-1142A was more potent than diphenoxylate and loperamide although species differences were noted. The ED50 for inhibition of castor oil-induced diarrhea was 1.8 mg/kg p.o. and the duration of action at 16 mg/kg p.o. was at least 6 h. Unlike diphenoxylate, WHR-1142A showed no tolerance.