The pharamacological profile of a novel selective vasopressin V₂ receptor antagonist, VP-343(N-[4-[[(2S, 3aR)-2-hydroxy-2, 3, 3a, 4-tetrahydropyrrolo[1, 2-a]quinoxalin-5(1H)-yl]carbonyl]Phenyl]-4'-methyl[1, 1'-biphenyl]-2-carboxamide) was characterized in several in vitro and in vivo rat models. The IC₅₀ values of VP-343 for vasopressin V_1A and V₂ receptors were 110 and 0.77 nM, respectively. VP-343 inhibited dose-dependently the pressor response to exogenous arginine vasopressin (AVP; 30 mU/kg, i.v.) in pithed rats, with an ID₅₀ value of 0.57 mg/kg(i.v.). VP-343 induced strong aquaresis in normal saline-loaded conscious rats. Antidiuretic activities of VP-343 have not been detected in AVP deficient Bratteleboro rats, showing its lack AVP V₂ agonistic activity. During repeated administration for 21 d (3 mg/kg, p.o.) and after recovery, the aquaretic action VP-343 still remained. In the aged (17 month) saline-loaded conscious rats study, VP-343 (3 mg/kg, p.o.) exhibited remarkable diuretic action. In a single dose oral toxicity study in mice, VP-343 did not produce any clinical signs and mortality at any of the tested doses.The results indicate that VP-343 is a potent, orally active selective V₂ receptor antagonist, suggesting that it can be expected to be useful as an aquaretic drug.