Compounds of general formula (I) wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and X are as defined herein are inhibitors of the epithelial sodium channel (ENaC) and are useful for the treatment or prevention respiratory diseases and conditions, skin conditions and ocular conditions.

##STR00001##

Compounds of general formula (I) wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and X are as defined herein are inhibitors of the epithelial sodium channel (ENaC) and are useful for the treatment or prevention respiratory diseases and conditions, skin conditions and ocular conditions.

##STR00001##

The present invention relates compounds of the formula:

##STR00001##

or pharmaceutically acceptable salts thereof, useful as sodium channel blockers, as well as compositions containing the same, processes for the preparation of the same, and therapeutic methods of use therefore in promoting hydration of mucosal surfaces and the treatment of diseases including cystic fibrosis, chronic obstructive pulmonary disease, asthma, bronchiectasis, acute and chronic bronchitis, emphysema, and pneumonia.

Provided herein are methods of increasing mucus clearance in a subject having decreased mucus clearance. Also provided are methods of treating or preventing a respiratory disorder.

Provided herein are methods of increasing mucus clearance in a subject having decreased mucus clearance. Also provided are methods of treating or preventing a respiratory disorder.

The present invention provides pyridine and pyrazine derivatives which restore or enhance the function of mutant and/or wild type CFTR to treat cystic fibrosis, primary ciliary dyskinesia, chronic bronchitis, chronic obstructive pulmonary disease, asthma, respiratory tract infections, lung carcinoma, xerostomia and keratoconjunctivitis sire, or constipation (IBS, IBD, opioid induced). Pharmaceutical compositions comprising such derivatives are also encompassed.

A compound and use thereof are provided. The compound of the invention has formula I shown below. Each variable in formula I, ##STR00001##
is defined in the specification. The invention also provides a method for treating renal and cardiac dysfunction. The method includes administering to a subject in need thereof an effective amount of the compound of the invention and a pharmaceutical acceptable salt and carrier.

The present invention relates to sodium channel blockers. The present invention also includes a variety of methods of treatment using these inventive sodium channel blockers.

A method is disclosed for blocking or reducing a physiological reaction in a mammal to the interaction of IgE antibodies present in said mammal upon contact with the corresponding antigen, by the administration to said mammal of a therapeutically effective amount of a neurotoxin (CnT) derived from Clostridia sp.

The present invention relates to methods of using compounds of Formula I,

##STR00001## wherein R.sup.1a, R.sup.1b, R.sup.2, R.sup.3, R.sup.4, W, Y, and Z are as described herein, and pharmaceutically acceptable salts thereof. The compounds are potentiators of Cystic Fibrosis Transmembrane conductance Regulator (CFTR). The invention also discloses pharmaceutical compositions comprising the compound, optionally in combination with additional therapeutic agents, and methods of potentiating, in mammals, including humans, CFTR by administration of the compounds. These compounds are useful for the treatment of cystic fibrosis (CF), asthma, bronchiectasis, chronic obstructive pulmonary disease (COPD), constipation, Diabetes mellitus, dry eye disease, pancreatitis, rhinosinusitis, Sj?gren's Syndrome, and other CFTR associated disorders.