Racecadotril: a new approach to the treatment of diarrhoea

Since enkephalins were discovered in 1975, it has become clear that they pl ay an antisecretory role in the gastrointestinal tract. Hence a rational re search programme was directed at the development of a drug that would prese rve these neurotransmitter peptides in the gut by preventing their inactiva tion. This research programme has resulted in the development of the enkeph alinase inhibitor, racecadotril. Preclinical studies have demonstrated the efficacy of racecadotril in two models of hypersecretory diarrhoea: infusio n of cholera toxin and castor oil-induced diarrhoea. Moreover, unlike loper amide, racecadotril did not prolong transit time in the small intestine or colon. Further experiments have shown that racecadotril does not promote ba cterial overgrowth in the small intestine. Racecadotril lacks any potential for neurotoxicity, and radiolabelled studies have demonstrated that the dr ug does not enter the brain after oral administration. No potential for abu se or physical dependence has been seen. It is concluded that racecadotril demonstrates specificity of antisecretory action on the gastrointestinal tr act without any adverse effect on gastrointestinal motility, and that the r esults of the preclinical studies indicate the potential usefulness in the treatment of hypersecretory diarrhoea in man. (C) 2000 Elsevier Science B.V . and International Society of Chemotherapy. All rights reserved.