Characterization of a novel non-peptide vasopressin V1 receptor antagonist (OPC-21268) in the rat

Abstract

A non-peptide, orally effective, vasopressin (AVP) V1 receptor antagonist 1-{1-[4-(3-acetylaminopropoxy) benzoyl]-4-piperidyl}-3,4-dihydro-2(1H)-quinolinone (OPC-21268) has recently been described. This paper reports the in-vitro and in-vivo characterization of OPC-21268 binding to vasopressin receptors in rat liver and kidney. OPC-21268 caused a concentration-dependent displacement of the selective V1 receptor antagonist radioligand, 125I-labelled [d(CH2)5,sarcosine7]AVP to V1 receptors in both rat liver and kidney medulla membranes. The concentration of OPC-21268 that displaced 50% of specific AVP binding (IC50) was 40 ± 3 nmol/l for liver V1 and 15 ± 2 nmol/l for kidney V1 receptors (mean..