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
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.