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EFFECTS OF AN ORALLY ACTIVE VASOPRESSIN V 1 RECEPTOR ANTAGONIST
Author(s) -
Burrell L. M.,
Phillips P. A.,
Stephenson J.,
Risvanis J.,
Hutchins AM.,
Johnston C. I.
Publication year - 1993
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1993.tb01713.x
Subject(s) - vasopressin , antagonist , radioligand , vasopressin receptor , endocrinology , medicine , vasopressin antagonists , receptor , receptor antagonist , neuropeptide , chemistry , biology
SUMMARY 1. This paper reports on the in vitro and in vivo characteristics of a non‐peptide vasopressin V 1 receptor antagonist 1‐{1‐[4‐(3‐acetylaminopropoxy)benzoyl]‐4‐piperidyl}‐3,4‐dihydro‐2(1H)‐quinolinone (OPC‐21268). 2. OPC‐21268 caused a concentration‐dependent displacement of the selective V 1 receptor antagonist radioligand, [ 125 I]‐[d(CH 2 ) 5 , sarcosine 7 ]AVP from vasopressin V 1 receptors in rat liver and kidney membranes, inhibitory concentration of 50% (IC 50 ) 4 ± 10‐ 8 , 0.3 mol/L liver and 1.5 ± 10‐ 8 , 0.2 mol/L kidney. OPC‐21268 had little effect on the selective V 2 antagonist radioligand [ 3 H]desGly‐NH 2 9 ‐d(CH 2 ) 5 [d‐Ileu 2 , Ileu 4 ]AVP binding to V 2 receptors in renal membranes (IC 50 > 10‐ 4 mol/L). 3. After oral administration to rats, OPC‐21268 was an effective V 1 antagonist to both liver and kidney V 1 receptors, in a dose‐dependent manner. 4. These studies confirm that OPC‐21268 is a potent non‐peptide, orally effective V 1 vasopressin receptor antagonist.