Lixivaptan (VPA-985) is an orally active and selective vasopressin receptor V2 antagonist(Ki = 2.3 nM)

V2 receptor (human):1.2 nM (IC50), V2 receptor (rat):2.3 nM (IC50)

Consistent with the development of a polycystic kidney phenotype, control PCK rats showed enlarged kidneys, extensive cyst formation, and early signs of serum creatinine elevation at 12 weeks of age.?Compared to controls, PCK rats treated with low-dose lixivaptan showed a 26% reduction in % kidney weight/body weight (p < 0.01);?a 54% reduction in kidney cystic score (p < 0.001), a histomorphometric measure of cystic burden;?a 23% reduction in kidney cAMP levels (p < 0.05), a biochemical marker of disease;?and a 13% reduction in plasma creatinine (p < 0.001), indicating preserved renal function.?These reductions were associated with 3-fold increases in 24-h urine output, demonstrating the potent aquaretic effect of lixivaptan[1].

Four-week old PCK rats were fed rodent chow with 0.5% lixivaptan (low dose) or 1% lixivaptan (high dose), or chow only (control) for 8 weeks.?Urine output was measured at weeks 7 and 10 of age.?Animals were killed at 12 weeks of age;?kidneys and livers were collected, weighted, and analyzed for cyclic adenosine 3',5'-monophosphate (cAMP) levels and cystic burden and fibrosis;?serum creatinine and sodium were measured[1].