| abstract |
pharmaceutical compounds and compositions for inhibiting unmediated antiport in the treatment of disorders associated with fluid retention or with salt overload and disorders of the gastrointestinal tract the present invention is directed to compounds and methods for the treatment of disorders associated with retention of fluid or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage kidney disease, liver disease, and fluid retention induced by peroxisome proliferator-activated receptor agonist agent (ppar). the present invention is also directed to compounds and methods for the treatment of hypertension. the present invention is also directed to compounds and methods for the treatment of disorders of the gastrointestinal tract, including the treatment or reduction of pain associated with disorders of the gastrointestinal tract. the methods generally comprise administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, which is developed to be substantially active in the gastrointestinal (gi) tract to inhibit the ions-mediated antiport therein. sodium and hydrogen ions. more particularly, the method comprises administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, which inhibits nhe-3, -2 and / or -8-mediated sodium ions and / or hydrogen ions in the gastrointestinal tract and is designed to be substantially impermeable to the epithelial cell layer, or more specifically to the epithelium of the gastrointestinal tract. |