The present study was undertaken to determine whether the non-
peptide V2
arginine vasopressin (AVP) antagonist 5-dimethylamino- 1[4-(2-methylbenzoylamino)benzoyl]-2,3,4,5-tetrahydro-1H-benzazepi ne hydrochloride (OPC-31260) produces water diuresis and improves
hyponatremia in patients with the syndrome of inappropriate secretion of
antidiuretic hormone (
SIADH). Eleven patients (9 males and 2 females, 64 +/- 3.5 yr) with
SIADH were included in the present protocol, which was comprised of 3 successive days. Day 1 was a control day, and on days 2 and 3
OPC-31260 was administered intravenously. Five blood and urine collections were made at 1-2 h intervals during the 6 h observation period each day. A single administration of 0.25 and 0.5 mg/kg
OPC-31260 increased the 4 h cumulative urine volume and decreased urinary osmolality to below 225 mOsm/kg H2O. Such a
diuretic effect was independent of an increase in urinary solute excretions. This aquaresis by 0.5 mg/kg
OPC-31260 caused a significant increase in serum
sodium level by approximately 3 mEq/L. The antagonistic effect of
OPC-31260 lasted for 4 h when it was given intravenously. These results indicate that
OPC-31260 is an effective therapeutic agent for
hyponatremia in patients with
SIADH.