Tolvaptan

Tolvaptan (OPC-41061) is a highly potent selective, competitive vasopressin V2-receptor antagonist with Ki of 0.43 nM, >200-fold more selective than for V1A-receptors; inhibits cAMP production induced by AVP with no intrinsic agonist activity; clearly produces dose-dependent aquaresis in rats; orally active. (In Vitro) :Tolvaptan (0-100 μM; 24-168 h) decreases the growth of HepG2 cells.Tolvaptan (20-100 μM; 24-48 h) induces cell death in HepG2 cells.Tolvaptan (0-100 μM; 24-48 h) affects cell cycle of HepG2 cells.Tolvaptan (0-100 μM; 24-48 h) causes DNA damage and induces apoptosis of HepG2 cells.Tolvaptan (0-100 μM; 24-48 h) decreases cyclins and CDKs, and increases γ-H2AX, PARP cleavage and LC3B-II in HepG2 cells.Tolvaptan (0-100 μM; 4-24 h) induces phosphorylation of JNK, ERK1/2 and p38 in HepG2 cells.Tolvaptan (0-100 μM; 24-28 h) induces autophagy of HepG2 cells. (In Vivo) :Tolvaptan (10 mg/kg; p.o. once per day for 22 days) improves cyclophosphamide (CP) -induced nephrotoxicity in rats.