Racecadotril versus loperamide - Antidiarrheal research revisited

Racecadotril is an enkephalinase inhibitor, presented as a purely antisecretory agent with advantages over the opiate-receptor agonist loperamide in the treatment of diarrhea. A critical review of the literature and the models used was performed. Although pretreatment with high doses of racecadotril reduced cholera toxin-induced secretion and although clinical efficacy was demonstrated in young infants-a population characterized by 10-fold higher plasma enkephalin concentrations compared with adults, the analysis calls into question the peripheral antisecretory selectivity and relative clinical efficacy. Conversely, loperamide can be proposed as an antisecretory agent at therapeutic concentrations. Its efficacy is well established in acute and chronic diarrhea. Current experimental and clinical comparative studies of both drugs have problems with regard to the selection of the doses, the validity of models, and/or the trial design. The conclusion is that more research is needed before reliable conclusions can be drawn on the place of racecadotril in diarrhea treatmen

Distinct Effects of Acetylcholine and Glucose On Ca-45 and Rb-86 Efflux From Mouse Pancreatic-islets

AbstractThe similarities between the effects of acetylcholine and glucose on phospholipid metabolism in pancreatic islet cells prompted the comparison of their effects on ionic fluxes. Acetylcholine (1 μM) consistently increased 45Ca2+ efflux from mouse islets, whereas glucose increased it in the presence, but decreased it in the absence of extracellular Ca2+. Acetylcholine consistently accelerated 86Rb+ efflux, and this effect was augmented by Ca2+ omission. On the other hand, glucose markedly inhibited 86Rb+ efflux, except when its concentration was raised from 10 to 15 mM in the presence of Ca2+. Unlike their effects on phospholipid metabolism, the ionic effects of the two insulin-secretagogues are thus very different

Therapeutic Advances in Functional Gastrointestinal Disease: Irritable Bowel Syndrome

Reported prevalence rates of irritable bowel syndrome (IBS) are between 8% to 20% in the US general population with an average medical expenditure of US$1.35 billion direct and US$205 million indirect costs. Current pathophysiologic theories are based on abnormalities of both the brain and gut, thus setting a new stage for current and future therapeutic approaches. There are numerous treatment options in IBS acting centrally and peripherally by influencing motility and visceral sensitivity. Clinical evidence is variable; however, newer emerging treatments are being evaluated using better-designed clinical trials. Accurate assessment of IBS drug efficacy is still hampered by heterogeneity of the IBS population. Novel methods such as pharmacogenomics or brain imaging may be helpful in the future to better understand and characterize IBS patient subtypes, and this in turn will lead to more specific and efficient therapeutic options. Patient subpopulation measurement of side effects is also a clinical challenge and further understanding could improve treatment efficacy by enhancing the patient compliance