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

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

与多囊肾表型的发展一致，对照的PCK大鼠表现出肾脏增大、广泛的囊肿形成以及12周龄时血清肌酐初期升高迹象。与对照组相比，接受低剂量lixivaptan治疗的PCK大鼠显示出以下改善：肾脏重量占体重百分比降低了26%（p < 0.01）；肾囊性评分降低了54%（p < 0.001），这是衡量囊肿负担的组织形态学指标；肾脏cAMP水平降低了23%（p < 0.05），这是疾病的生化标志；血浆肌酐降低了13%（p < 0.001），表明肾功能得到保留。这些降低与24小时尿产量增加3倍相关，显示了lixivaptan的强大利尿效应[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].