Last reviewed 2026-04-23 · How we verify

NPSP558

NPSP558 is a selective vasopressin V1a receptor antagonist that blocks vasopressin signaling to reduce aquaporin-2 water channel expression and increase urine output.

NPSP558 is a selective vasopressin V1a receptor antagonist that blocks vasopressin signaling to reduce aquaporin-2 water channel expression and increase urine output. Used for Acute decompensated heart failure, Hyponatremia.

At a glance

Mechanism of action

By antagonizing the V1a receptor on vascular smooth muscle and other tissues, NPSP558 prevents vasopressin-mediated vasoconstriction and reduces water reabsorption in the kidney collecting duct. This dual mechanism makes it potentially useful in conditions characterized by excessive vasopressin activity or fluid retention, such as heart failure and hyponatremia.

Approved indications

• Acute decompensated heart failure
• Hyponatremia

Common side effects

• Hypernatremia
• Thirst
• Polyuria
• Headache

Key clinical trials

• Study of Safety and Efficacy of a rhPTH[1-84] of Fixed Doses of 25 and 50 mcg in Adults With Hypoparathyroidism (RELAY) (PHASE3)
• A Study to Investigate the Safety and Tolerability of NPSP558, for the Treatment of Adults With Hypoparathyroidism - A Clinical Extension Study in Hungary (PHASE3)
• Use of NPSP558 in the Treatment of Hypoparathyroidism (PHASE3)
• A Open-label Study Investigating the Safety and Tolerability of NPSP558, a Recombinant Human Parathyroid Hormone (rhPTH [1-84]), for the Treatment of Adults With Hypoparathyroidism - A Clinical Extension Study (RACE) (PHASE3)
• ADD-ON Study to Existing Hypoparathyroidism Studies (PHASE3)

Primary sources

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