The therapeutic efficacy of VP-343, a selective vasopressin V2 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,4-tetrahydropyrrolo[1,2-a]qunoxalin-5(1H)-yl]phenyl]-4'-methyl[1,1'-biphenyl]-2-carboxamide), a selective vasopressin V2 receptor antagonist, using the experimental SIADH (syndrome of inappropriate secretion of antidiuretic hormone) rat model. In the model, which was accomplished by administering continuously 1-desamino-8-D-arginine vasopressin (DDAVP), serum sodium levels (S(Na)) and serum osmolarity levels (S(Osm)) significantly and remarkably decreased, which was accompanied with hyper-osmolarity of urine and oliguria. VP-343 increased rapidly and dose-dependently S(Na) and S(Osm). VP-343 exhibited marked diuretic action and decreased urine osmolarity dose-dependently. In the SIADH rat model, all serum levels of chloride, calcium, creatinine, total cholesterol, and uric acid decreased when compared with normal levels. VP-343 increased all serum levels of chloride, calcium, and total cholesterol. These results indicate that VP-343 has efficacy to normalize the abnormalities in DDAVP-induced SIADH.
AuthorsA Naito, H Hasegawa, T Kurasawa, Y Ohtake, H Matsukawa, Y Ezure, Y Tsuriya, K Koike, K Shigenobu
JournalBiological & pharmaceutical bulletin (Biol Pharm Bull) Vol. 23 Issue 11 Pg. 1323-7 (Nov 2000) ISSN: 0918-6158 [Print] Japan
PMID11085360 (Publication Type: Journal Article)
Chemical References
  • Antidiuretic Hormone Receptor Antagonists
  • Pyrroles
  • Quinoxalines
  • Renal Agents
  • VP 343
  • Sodium
  • Deamino Arginine Vasopressin
  • Animals
  • Antidiuretic Hormone Receptor Antagonists
  • Deamino Arginine Vasopressin (pharmacology)
  • Inappropriate ADH Syndrome (drug therapy, urine)
  • Male
  • Osmolar Concentration
  • Pyrroles (therapeutic use)
  • Quinoxalines (therapeutic use)
  • Rats
  • Rats, Sprague-Dawley
  • Renal Agents (pharmacology)
  • Sodium (blood)
  • Urination (drug effects)
  • Urine (chemistry)

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