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Title: Characterization of a novel non-peptide vasopressin V1 receptor antagonist (OPC-21268) in the rat.
Austin Authors: Burrell, Louise M ;Phillips, P A;Stephenson, J;Risvanis, John;Hutchins, A M;Johnston, Colin I
Affiliation: Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia
Issue Date: 1-Aug-1993
Publication information: The Journal of Endocrinology; 138(2): 259-66
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 +/- S.E.M.; n = 3). OPC-21268 had little effect on the selective V2 antagonist radioligand [3H]desGly-NH2(9)]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.
Gov't Doc #: 8228734
Type: Journal Article
Subjects: Animals
Antidiuretic Hormone Receptor Antagonists
Arginine Vasopressin.metabolism
Dose-Response Relationship, Drug
In Vitro Techniques
Kidney Medulla.metabolism
Protein Binding
Radioligand Assay
Rats, Sprague-Dawley
Time Factors
Appears in Collections:Journal articles

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