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Acute aquaresis by the nonpeptide arginine vasopressin (AVP) antagonist OPC-31260 improves hyponatremia in patients with syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

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 syndr...

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Published in:The journal of clinical endocrinology and metabolism 1997-04, Vol.82 (4), p.1054-1057
Main Authors: SAITO, T, ISHIKAWA, S.-E, ABE, K, KAMOI, K, YAMADA, K, SHIMIZU, K, SARUTA, T, YOSHIDA, S
Format: Article
Language:English
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Summary: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.
ISSN:0021-972X
1945-7197
DOI:10.1210/jc.82.4.1054