Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0740441 (acute diarrhea)
 2,275 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetorphan is an orally active inhibitor of enkephalinase (EC 3.4.24.11) with antidiarrhoeal activity in rodents apparently through protection of endogenous enkephalins and a purely antisecretory mechanism. Its antidiarrhoeal activity in man was assessed in an experimental model of cathartic induced secretory diarrhoea as well as in acute diarrhoea of presumed infectious origin. In six healthy volunteers receiving castor oil and pretreated with acetorphan or placebo in a crossover controlled trial, the drug significantly decreased the number and weight of stools passed during 24 hours. About 200 outpatients with severe acute diarrhoea (more than five stools per day) were included in a randomised double blind study of acetorphan against placebo. The significant antidiarrhoeal activity of acetorphan was established using a variety of criteria: (i) the duration of both diarrhoea and treatment were diminished; (ii) no acetorphan treated patient withdrew from the study whereas five dropped out because of worsening in the placebo group; (iii) the frequency of symptoms associated with diarrhoea--for example, abdominal pain or distension, nausea and anorexia--remaining after two weeks was nearly halved; (iv) using visual analogue scales acetorphan treatment was found more effective than placebo by both investigators and patients. There was statistically no significant difference between acetorphan and placebo in respect of side effects, particularly constipation, which often accompanies the antidiarrhoeal activity of mu opioid receptor agonists this difference is attributable to the lack of antipropulsive activity of acetorphan in man. The efficacy and tolerance of acetorphan suggest that enkephalinase inhibition may represent a novel therapeutic approach for the symptomatic management of acute secretory diarrhoea without impairing intestinal transit.
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PMID:Effects of acetorphan, an enkephalinase inhibitor, on experimental and acute diarrhoea. 847 99

The antidiarrhoeal properties of acetorphan, an inhibitor of enkephalinase (EC 3.4.24.11) that prevents endogenous enkephalin degradation, and loperamide, a mu opiate receptor agonist, were compared. The double-blind study included 69 patients with acute diarrhoea of presumed infectious origin, allocated at random to two parallel groups. Acetorphan and loperamide were both rapidly and similarly effective, diarrhoea resolving in both cases in nearly 2 days. With acetorphan, however, abdominal distension vanished significantly more rapidly, and reactive constipation was less frequent (8% versus 31% with loperamide). These differences can be accounted for by the distinct mechanisms of antidiarrhoeal activity of the two drugs--that is, primary antitransit effect for loperamide and antisecretory activity for acetorphan.
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PMID:The enkephalinase inhibitor, acetorphan, in acute diarrhoea. A double-blind, controlled clinical trial versus loperamide. 848 68

Racecadotril, via its active metabolite thiorphan, is an inhibitor of the enzyme neutral endopeptidase (NEP, EC 3.4.24.11), thereby increasing exposure to NEP substrates including enkephalins and atrial natriuretic peptide (ANP). Upon oral administration racecadotril is rapidly and effectively converted into the active metabolite thiorphan, which does not cross the blood-brain-barrier. Racecadotril has mainly been tested in animal models and patients of three therapeutic areas. As an analgesic the effects of racecadotril across animal models were inconsistent. In cardiovascular diseases such as hypertension or congestive heart failure results from animal studies were promising, probably related to increased exposure to ANP, but clinical results have not shown substantial therapeutic benefit over existing treatment options in cardiovascular disease. In contrast, racecadotril was consistently effective in animal models and patients with various forms of acute diarrhea by inhibiting pathologic (but not basal) secretion from the gut without changing gastro-intestinal transit time or motility. This included studies in both adults and children. In direct comparative studies with loperamide in adults and children, racecadotril was at least as effective but exhibited fewer adverse events in most studies, particularly less rebound constipation. Several guidelines recommend the use of racecadotril as addition to oral rehydration treatment in children with acute diarrhea.
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PMID:A comprehensive review of the pharmacodynamics, pharmacokinetics, and clinical effects of the neutral endopeptidase inhibitor racecadotril. 2266 49

Acute diarrhoea is a leading cause of morbidity and mortality in the paediatric population. Racecadotril is an antisecretory drug recommended as an adjuvant antidiarrhoeal treatment.In the small bowel, the enzyme neutral endopeptidase (NEP) inhibits the action of enkephalins, which prevent water and electrolyte hypersecretion. By inhibiting NEP, racecadotril allows enkephalins to exhibit their antisecretory effects. Consequently, racecadotril reduces the secretion of water and electrolytes in the small intestine, without having an effect on intestinal motility. No serious adverse events related to racecadotril have been reported.Racecadotril has proven its efficacy as an adjuvant antidiarrhoeal drug with a good safety profile. Its addition to oral rehydration solution (ORS) appears clinically beneficial and potentially leads to health care savings.
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PMID:Drugs in Focus: The Use of Racecadotril in Paediatric Gastrointestinal Disease. 3197 9