The therapeutic efficacy of VP-343, a selective vasopressin V-2 receptor antagonist, in the experimental SIADH rat model

The aim of this work is to investigate the therapeutic efficacy of VP-343 ( (N-[4-[[(2S,3aR)-2-hydroxy-2,3,3a, 1-tetrahydropyrrolo[1,2-a]qunoxalin-5(1H )-yl]phenyl]-4'-methyl[1,1'-biphenyl]-2-carboxamide), a selective vasopress in V-2 receptor antagonist, using the experimental SIADH (syndrome of inapp ropriate secretion of antidiuretic hormone) rat model. In the model, which was accomplished by administering continuously 1-desamino-8-D-arginine vaso pressin (DDAVP), serum sodium levels (S-Na,,) and serum osmolarity levels ( S-Osm) significantly and remarkably decreased, which was accompanied with h yper-osmolarity of urine and oliguria. VP-343 increased rapidly and dose-de pendently S-Na and S-Osm. VP-343 exhibited marked diuretic action and decre ased urine osmolarity dose-dependently, In the SIADH rat model, all serum l evels of chloride, calcium, creatinine, total cholesterol, and uric acid de creased when compared with normal levels. VP-343 increased all serum le, el s of chloride, calcium, and total cholesterol, These results indicate that VP-343 has efficacy to normalize the abnormalit ies in DDAVP-induced SIADH.