Potent aquaretic agent. A novel nonpeptide selective vasopressin 2 antagonist (OPC-31260) in men

J Clin Invest. 1993 Dec;92(6):2653-9. doi: 10.1172/JCI116881.


Solute-free water diuretics (aquaretics) by antagonizing hydrosmotic vasopressin receptors (V2) may be useful in treating water-retaining diseases. The effects of intravenous administration of a newly developed nonpeptide, selective V2 antagonist, OPC-31260, at doses ranging from 0.017 to 1.0 mg/kg to groups of healthy, normally hydrated men were compared with those of 0.33 mg/kg furosemide and placebo. OPC-31260 increased the hypotonic urine volume dose dependently for the first 4 h, while furosemide induced sodium diuresis for 2 h. The absolute increase in the cumulative response in the urine to the highest doses of OPC-31260 was not significantly different from that to furosemide. The higher doses of OPC-31260 rapidly lowered urine osmolality for 2 h, particularly between minutes 15 and 45 (e.g., 1.0-mg/kg dose: 63 +/- 2 mOsm/kg in urine collected between minutes 30 and 45). In a marked hypotonic diuresis, mean free water clearance of the 4-h urine increased dose proportionally into the positive range, reaching 1.80 +/- 0.21 ml/min at 1.0 mg/kg. Whereas furosemide induced marked Na and K diuresis, OPC-31260 increased urinary Na excretion only slightly. At 4 h, 0.75 and 1.0 mg/kg of OPC-31260 almost doubled the plasma arginine vasopressin; and the higher doses increased plasma osmolality and plasma Na slightly, but did not alter plasma K, blood pressure, or heart rate. OPC-31260 thus safely induced a potent aquaretic effect in men.

MeSH terms

  • Adult
  • Aldosterone / blood
  • Analysis of Variance
  • Antidiuretic Hormone Receptor Antagonists*
  • Arginine Vasopressin / blood*
  • Benzazepines / pharmacology*
  • Blood Pressure / drug effects
  • Chlorides / urine
  • Diuresis / drug effects*
  • Diuretics / pharmacology*
  • Dose-Response Relationship, Drug
  • Furosemide / pharmacology
  • Heart Rate / drug effects
  • Humans
  • Male
  • Osmolar Concentration
  • Potassium / urine
  • Renin / blood
  • Sodium / blood
  • Sodium / urine
  • Time Factors
  • Urine


  • Antidiuretic Hormone Receptor Antagonists
  • Benzazepines
  • Chlorides
  • Diuretics
  • Arginine Vasopressin
  • mozavaptan
  • Aldosterone
  • Furosemide
  • Sodium
  • Renin
  • Potassium