Aquaretic effects of the nonpeptide V2 antagonist OPC-31260 in hydropenic humans.

The antidiuretic action of arginine vasopressin (AVP) is mediated by interaction with renal V2 receptors. A nonpeptide V2 receptor antagonist, OPC-31260, has recently been developed. In this study, the effects of OPC-31260 on the excretion of water and electrolytes were investigated in normal subjects who were under water restriction. Since the clinical circumstances in which a V2 antagonist would be useful generally would be in patients with concentrated urine, a hydropenic state with nearly maximally concentrated urine was selected as the experimental condition. Intravenous injection of OPC-31260 caused an increase in urine volume and a decrease in urine osmolality in a dose dependent manner without any significant changes in the excretion of sodium and other electrolytes. A high dose of OPC-31260 (1 mg/kg body wt) caused free water excretion equivalent to that obtained during maximum diuresis after water loading, followed by an increase in plasma sodium and AVP concentration. Excretion of urea increased transiently during diuresis. Thus, OPC-31260 is demonstrated to be the first V2 antagonist which exhibits water diuresis (aquaresis) in hydropenic humans with endogenous AVP secretion and maximally concentrated urine. The drug will be useful as an aquaretic in the treatment of some types of hyponatremia where there is excess AVP and water retention.