title: A novel vasopressin dual V1A/V2 receptor antagonist, conivaptan hydrochloride, improves hyponatremia in rats with syndrome of inappropriate secretion of antidiuretic hormone (SIADH).
abstract: 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.
authors.affiliation: Pharmacology Research Laboratories, Drug Discovery Research, Astellas Pharma Inc., Tsukuba, Ibaraki, Japan. kouichi.wada@jp.astellas.com
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Wada
authors.forename: Utane
authors.initials: U
authors.lastname: Matsukawa
authors.forename: Akira
authors.initials: A
authors.lastname: Fujimori
authors.forename: Yukinori
authors.initials: Y
authors.lastname: Arai
authors.forename: Katsumi
authors.initials: K
authors.lastname: Sudoh
authors.forename: Masao
authors.initials: M
authors.lastname: Sasamata
authors.forename: Keiji
authors.initials: K
authors.lastname: Miyata
mesh_terms: D000818:Animals; D065092:Antidiuretic Hormone Receptor Antagonists; D001127:Arginine Vasopressin; D001552:Benzazepines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004232:Diuretics / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005665:Furosemide / Q000494:pharmacology; D007010:Hyponatremia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D007177:Inappropriate ADH Syndrome / Q000097:blood / Q000139:chemically induced / Q000150:complications*; D007275:Injections, Intravenous; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood; D014867:Water; D014882:Water-Electrolyte Balance / Q000187:drug effects*
chemical_list: D065092:Antidiuretic Hormone Receptor Antagonists; D001552:Benzazepines; D004232:Diuretics; D014867:Water; C106389:conivaptan; D001127:Arginine Vasopressin; D005665:Furosemide; D012964:Sodium; D011188:Potassium