Hyponatremia is a condition in which the sodium concentration in the blood is too low, often caused by conditions that cause the body to retain too much water. Sodium is critical for maintaining blood pressure and for the proper functioning of nerves and muscles.

When blood sodium levels drop, cells will absorb water to balance sodium levels. When this happens to brain cells, it can lead to dangerous brain swelling. Many of the major symptoms—such as confusion, headaches, or hallucinations—are caused by this swelling. If sodium levels fall especially quickly—a condition called acute hyponatremia—rapid brain swelling can lead to coma or death.

Hyponatremia treatment may include water restriction, hypertonic saline, intravenous administration of a mixed V1/V2 antagonist for certain hospitalized patients, and other medications. However, most of these approaches are either poorly tolerated, associated with significant risks or have minimal impact on correcting the abnormally low level of serum sodium. There is a clear need for an effective, well tolerated, oral treatment for hyponatremia.

Heart failure is a major cause of hyponatremia. About one-fourth of the 5 million U.S. heart failure patients each year develop hyponatremia. Other causes of hyponatremia include burns, diuretic medications, kidney disease, marathon running, anorexia nervosa, liver cirrhosis, syndrome of inappropriate hormone secretion (SIADH), vomiting and diarrhea.