Racecadotril: a new approach to the treatment of diarrhoea.
Since enkephalins were discovered in 1975, it has become clear that they play an antisecretory role in the gastrointestinal tract. Hence a rational research programme was directed at the development of a drug that would preserve these neurotransmitter peptides in the gut by preventing their inactivation. This research programme has resulted in the development of the enkephalinase inhibitor, racecadotril. Preclinical studies have demonstrated the efficacy of racecadotril in two models of hypersecretory diarrhoea: infusion of cholera toxin and castor oil-induced diarrhoea. Moreover, unlike loperamide, racecadotril did not prolong transit time in the small intestine or colon. Further experiments have shown that racecadotril does not promote bacterial overgrowth in the small intestine. Racecadotril lacks any potential for neurotoxicity, and radiolabelled studies have demonstrated that the drug does not enter the brain after oral administration. No potential for abuse or physical dependence has been seen. It is concluded that racecadotril demonstrates specificity of antisecretory action on the gastrointestinal tract without any adverse effect on gastrointestinal motility, and that the results of the preclinical studies indicate the potential usefulness in the treatment of hypersecretory diarrhoea in man.
Schwartz
J C
JC
Unité de Neurobiologie et Pharmacologie Moléculaire (U-109) de l'INSERM, Centre Paul Broca, 2ter rue d'Alésia, 75014, Paris, France. u109@broca.inserm.fr
D000818:Animals; D000930:Antidiarrheals / Q000627:therapeutic use*; D003967:Diarrhea / Q000188:drug therapy*; D004285:Dogs; D051381:Rats; D015244:Thiorphan / Q000031:analogs & derivatives* / Q000627:therapeutic use
D000930:Antidiarrheals; C049331:racecadotril; D015244:Thiorphan