A novel vasopressin dual V1A/V2 receptor antagonist, conivaptan hydrochloride, improves hyponatremia in rats with syndrome of inappropriate secretion of antidiuretic hormone (SIADH).

Publisher: Pharmaceutical Society of Japan Country of Publication: Japan NLM ID: 9311984 Publication Model: Print Cited Medium: Print ISSN: 0918-6158 (Print) Linking ISSN: 09186158 NLM ISO Abbreviation: Biol Pharm Bull Subsets: MEDLINE

Original Publication: Tokyo : Pharmaceutical Society of Japan, c1993-

Antidiuretic Hormone Receptor Antagonists*; Benzazepines/*pharmacology ; Diuretics/*pharmacology ; Hyponatremia/*drug therapy ; Inappropriate ADH Syndrome/*complications ; Water-Electrolyte Balance/*drug effects; Animals ; Arginine Vasopressin ; Benzazepines/administration & dosage ; Benzazepines/therapeutic use ; Disease Models, Animal ; Diuretics/therapeutic use ; Dose-Response Relationship, Drug ; Furosemide/pharmacology ; Hyponatremia/blood ; Hyponatremia/etiology ; Hyponatremia/physiopathology ; Inappropriate ADH Syndrome/blood ; Inappropriate ADH Syndrome/chemically induced ; Injections, Intravenous ; Male ; Osmolar Concentration ; Potassium/blood ; Rats ; Rats, Wistar ; Sodium/blood ; Water

We investigated the effects of intravenous administration of conivaptan hydrochloride, a dual vasopressin V1A and V2 receptor antagonist, on blood electrolytes and plasma osmolality in rats with an experimental syndrome of inappropriate secretion of antidiuretic hormone (SIADH). The experimental SIADH rat model was developed by means of continuous administration of arginine vasopressin (AVP) via a subcutaneously implanted osmotic mini pump, and hyponatremia was induced by additional water loading. This model possesses similar characteristics to those observed in patients with SIADH, specifically decreases in blood sodium concentration and plasma osmolality. In this experimental model, intravenous administration of conivaptan (0.1, 1 mg/kg) significantly increased blood sodium concentration and plasma osmolality. On the other hand, intravenous administration of furosemide (10 mg/kg) did not increase either blood sodium concentration or plasma osmolality in the SIADH rats. Moreover, furosemide significantly lowered blood potassium concentration. These results show that conivaptan improves hyponatremia in rats with SIADH, supporting the therapeutic potential of conivaptan in treatment of patients with hyponatremia associated with SIADH.

0 (Antidiuretic Hormone Receptor Antagonists)
0 (Benzazepines)
0 (Diuretics)
059QF0KO0R (Water)
0NJ98Y462X (conivaptan)
113-79-1 (Arginine Vasopressin)
7LXU5N7ZO5 (Furosemide)
9NEZ333N27 (Sodium)
RWP5GA015D (Potassium)

Date Created: 20070105 Date Completed: 20070313 Latest Revision: 20190720

20221213

10.1248/bpb.30.91

17202666