Vasopressin plays a central role in regulating body fluid homeostasis, serum osmolality and vascular tone. In response to elevated serum osmolality,
vasopressin acts on V2 renal receptors increasing water reabsorption and causing serum
sodium to decrease. Pathological conditions characterized by abnormally elevated
vasopressin levels such as
heart failure (HF) or syndrome of inappropriate
antidiuretic hormone (
SIADH) can result in
hyponatremia.
Tolvaptan is a new selective nonpeptide
vasopressin V2 receptor antagonist that has shown to rapidly normalize serum
sodium concentrations in hyponatremic patients. In patients with
congestive heart failure (CHF) and symptoms of volume overload,
tolvaptan prompted rapid free water elimination and improved short-term signs and symptoms of HF, although no effect on long-term mortality or HF-related morbidity was observed. Data from phase III studies including over 5,000 patients have demonstrated that
tolvaptan is a safe and well tolerated
vasopressin receptor antagonist, whose long-term use is not associated with adverse outcomes.
Tolvaptan has been recently approved for the treatment of
hyponatremia and a marketing authorization application has been filed for the treatment of CHF.