Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist.

摘要: SR 121463A, a potent and selective, orally active, nonpeptide vasopressin V2 receptor antagonist, has been characterized in several vitro vivo models. This compound displayed highly competitive selective affinity for receptors rat, bovine human kidney (0.6 < or = Ki [nM] 4.1). In this latter preparation, 121463A potently antagonized arginine (AVP)-stimulated adenylyl cyclase activity (Ki 0.26+/-0.04 nM) without any intrinsic agonistic effect. autoradiographic experiments performed rat sections, displaced [3H]AVP labeling especially the medullo-papillary region confirmed that it is suitable tool mapping receptors. comparison, OPC-31260, showed much lower animal renal efficacy to inhibit vasopressin-stimulated 10 nanomolar range). Moreover, OPC-31260 exhibited poor selectivity profile can be considered as V2/V1a ligand. normally hydrated conscious rats, induced powerful aquaresis after intravenous (0.003-0.3 mg/kg) oral (0.03-10 administration. The effect was dose-dependent lasted about 6 hours at dose of 3 mg/kg p.o. had similar aquaretic but with markedly efficacy. action purely no changes urine Na+ K+ excretions unlike known diuretic agents such furosemide hydrochlorothiazide. addition, antidiuretic properties have detected vasopressin-deficient Brattleboro rats. Thus, most active antagonist yet described could exploring therapeutical usefulness blocker water-retaining diseases.