Mozavaptan (OPC-31260) is a benzazepine derivative and a potent, selective, competitive and orally active vasopressin V₂ receptor antagonist with an IC₅₀ of 14 nM. Mozavaptan shows ~85-fold selectivity for V₂ receptor over V₁ receptor (IC₅₀ of 1.2 μM), and can antagonize the antidiuretic action of arginine vasopressin (AVP) in vivo. Mozavaptan has the potential for hyponatremia, syndrome of inappropriate antidiuretic hormone (SIADH), and congestive heart failure treatment^[1][2]. IC50 & Target: IC50: 14 nM (Vasopressin V₂ receptor); 1.2 μM (Vasopressin V₁ receptor)^[1] In Vitro: Mozavaptan (OPC-31260) inhibits AVP binding to binding to rat liver (V1 receptor) and kidney (V2 receptor) plasma membranes in a competitive manner and that it is about 100 times more selective for V2 receptors. K_d value for [3H]-AVP in rat liver is 1.1 nM; in rat kidney is 1.38 nM. The K_d of [3H]-AVP is reduced significantly in both rat liver and kidney in the presence of Mozavaptan (K_d of 2.47 nM and 5.51 nM for V1 receptor at the doses of 0.3 μM and 1 μM.respectively; K_d of 2.4 nM and 4.03 nM for V2 receptor at the doses of 0.3 μM and 1 μM.respectively)^[1]. In Vivo: Mozavaptan (OPC-31260; 1-30 mg/kg; oral administration; hydrated conscious rats) treatment dose-dependently increases urine flow and decreased urine osmolality^[1].
Mozavaptan (OPC-31260; 10-100 μg/kg; intravenous injection; male Sprague-Dawley rats) treatment inhibits the antidiuretic action of exogenously administered arginine vasopressin (AVP) in water-loaded, alcohol-anaesthetized rats in a dose-dependent manner^[1].