COMPOUNDS AND METHODS FOR INHIBITING NHE-MEDIATED ANTIPORT IN THE TREATMENT OF DISORDERS ASSOCIATED WITH FLUID RETENTION OR SALT OVERLOAD AND GASTROINTESTINAL TRACT DISORDERS
The present invention relates to body fluid retention or salts such as heart failure (especially congestive heart failure), chronic kidney disease, end-stage kidney disease, liver disease, and peroxisome proliferative factor-activated receptor (PPAR) gamma agonist-induced fluid retention. It relates to compounds and methods for treating disorders associated with overload. The invention also relates to compounds and methods for treating hypertension. The invention also relates to compounds and methods for the treatment of gastrointestinal disorders, comprising the treatment or reduction of pain associated with gastrointestinal disorders. The method generally comprises a compound designed to be substantially active in inhibiting the NHE-mediated reverse transport of sodium ions and hydrogen ions therein within the gastrointestinal (GI) tract to a mammal in need, or a pharmaceutical composition comprising such a compound. It includes administering a pharmaceutically effective amount of. More particularly, the method inhibits the NHE-3, -2 and/or -8-mediated reverse transport of sodium ions and hydrogen ions in the GI tract to mammals in need, and the layer of epithelial cells, more particularly the epithelial layer of the GI tract. And administering a pharmaceutically effective amount of a compound designed to be substantially impermeable to or a pharmaceutical composition comprising such compound. As a result of the compound being substantially impermeable, it is not absorbed and is therefore essentially systemically non-bioavailable so that exposure of other internal organs (eg, liver, heart, brain, etc.) to it is limited. The present invention also provides a method of providing a mammal with the ability of the combination to act as described above and to sequester fluids and/or salts present in the GI tract by administering such compounds together with a fluid-absorbing polymer. About.본 발명은 심부전 (특히, 울혈성 심부전), 만성 신장질환, 말기 신장 질환, 간 질환, 및 퍼옥시좀 증식인자-활성화된 수용체 (PPAR) 감마
