Tolvaptan is a selective and oral active antagonist of arginine vasopressin (AVP) V2-receptor with Ki value of 0.43nM [1].
Tolvaptan is a nonpeptide AVP V2-receptor antagonist. It prevents AVP from binding to V2-receptor. In the in vitro binding assay using HeLa cells expressing human AVP receptor subtypes, tolvaptan shows inhibitory activity against V2 and V1a receptors with Ki values of 0.43nM and 12.3nM, respectively. The V1b receptor and 30 other receptors or ion channels are not sensitive to tolvaptan, indicating that tolvaptan is selective to V2-receptor. Tolvaptan also inhibits the production of cAMP induced by AVP with IC50 value of 8nM [1].
In animal models, the tolvaptan induced aquaresis results in increased urine volume and serum sodium. In rat models of acute and chronic hyponatremia, administration of tolvaptan increases plasma sodium levels and decreases the mortality [1].
References:
[1] Miyazaki T, Fujiki H, Yamamura Y, et al. Tolvaptan, an Orally Active Vasopressin V2-Receptor Antagonist-Pharmacology and Clinical Trials. Cardiovascular drug reviews, 2007, 25(1): 1-13.