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

L. M. Burrell, P. A. Phillips, J. Stephenson, J. Risvanis, A. M. Hutchins, C. I. Johnston

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22 Citations (Scopus)


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 ± S.E.M.; n = 3). OPC-21268 had little effect on the selective V2 antagonist radioligand [3H]desGly-NH29[d(CH2)5,D-Ile2,Ile4] AVP binding to V2 receptors in renal medulla membranes (IC50>0.1 mmol/l). After oral administration to rats, OPC-21268 was an effective V1 antagonist in a time- and dose-dependent manner. Binding kinetic studies showed that OPC-21268 acted as a competitive antagonist at the liver V1 receptor in vitro and in vivo, in addition to its in-vitro competitive effects at the renal V1 receptor. OPC-21268 shows promise as an orally active V1 antagonist.

Original languageEnglish
Pages (from-to)259-266
Number of pages8
JournalJournal of Endocrinology
Issue number2
Publication statusPublished - Aug 1993
Externally publishedYes


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