CHARACTERIZATION OF A NOVEL AQUARETIC AGENT, OPC-31260, AS AN ORALLY EFFECTIVE, NONPEPTIDE VASOPRESSIN V2-RECEPTOR ANTAGONIST

Citation
Y. Yamamura et al., CHARACTERIZATION OF A NOVEL AQUARETIC AGENT, OPC-31260, AS AN ORALLY EFFECTIVE, NONPEPTIDE VASOPRESSIN V2-RECEPTOR ANTAGONIST, British Journal of Pharmacology, 105(4), 1992, pp. 787-791
Citations number
20
Language
INGLESE
art.tipo
Article
ISSN journal
0007-1188
Volume
105
Issue
4
Year of publication
1992
Pages
787 - 791
Database
ISI
SICI code
0007-1188(1992)105:4<787:COANAA>2.0.ZU;2-S
Abstract
1 OPC-31260, a benzazepine derivative, has been studied for its abilit y to antagonize the binding of arginine vasopressin (AVP) to receptors in rat liver (V1) and kidney (V2) plasma membranes, for antagonism of the antidiuretic action of AVP in alcohol-anaesthetized rats and for diuretic action in conscious normal rats. 2 OPC-31260 caused a competi tive displacement of [H-3]-AVP binding to both V1 and V2 receptors wit h IC50 values of 1.2 +/- 0.2 x 10(-6) M and 1.4 +/- 0.2 x 10(-8) M, re spectively. 3 OPC-31260 at doses of 10 to 100-mu-g kg-1, i.v., inhibit ed the antidiuretic action of exogenously administered AVP in water-lo aded, alcohol-anaesthetized rats in a dose-dependent manner. OPC-31260 did not exert an antidiuretic activity suggesting that it is not a pa rtial V2 receptor agonist. 4 After oral administration at doses of 1 t o 30 mg kg-1 in normal conscious rats, OPC-31260 dose-dependently incr eased urine flow and decreased urine osmolality. The diuretic action o f OPC-31260 was characterized as aquaresis, the mode of diuretic actio n being different from previously known diuretic agents such as furose mide, hydrochlorothiazide and spironolactone. 5 The results indicate t hat OPC-31260 is a selective V2 receptor antagonist and behaves as an aquaretic agent. OPC-31260 will be a useful tool in studying the physi ological role of AVP and in the treatment of various conditions charac terized by water retention.