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Characterization of a novel aquaretic agent, OPC‐31260, as an orally effective, nonpeptide vasopressin V 2 receptor antagonist
Author(s) -
Yamamura Yoshitaka,
Ogawa Hidenori,
Yamashita Hiroshi,
Chihara Tomihiko,
Miyamoto Hisashi,
Nakamura Shigeki,
Onogawa Toshiyuki,
Yamashita Tatsuya,
Hosokawa Tetsumi,
Mori Toyoki,
Tominaga Michiaki,
Yabuuchi Youichi
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb09058.x
Subject(s) - endocrinology , vasopressin , medicine , antidiuretic , diuretic , antagonist , vasopressin receptor , chemistry , urine osmolality , receptor , pharmacology
1 OPC‐31260, a benzazepine derivative, has been studied for its ability to antagonize the binding of arginine vasopressin (AVP) to receptors in rat liver (V 1 ) and kidney (V 2 ) 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 competitive displacement of [ 3 H]‐AVP binding to both V 1 and V 2 receptors with IC 50 values of 1.2 ± 0.2 × 10 −6 m and 1.4 ± 0.2 × 10 −8 m , respectively. 3 OPC‐31260 at doses of 10 to 100 μg kg −1 , i.v., inhibited the antidiuretic action of exogenously administered AVP in water‐loaded, alcohol‐anaesthetized rats in a dose‐dependent manner. OPC‐31260 did not exert an antidiuretic activity suggesting that it is not a partial V 2 receptor agonist. 4 After oral administration at doses of 1 to 30 mg kg −1 in normal conscious rats, OPC‐31260 dose‐dependently increased urine flow and decreased urine osmolality. The diuretic action of OPC‐31260 was characterized as aquaresis, the mode of diuretic action being different from previously known diuretic agents such as furosemide, hydrochlorothiazide and spironolactone. 5 The results indicate that OPC‐31260 is a selective V 2 receptor antagonist and behaves as an aquaretic agent. OPC‐31260 will be a useful tool in studying the physiological role of AVP and in the treatment of various conditions characterized by water retention.