Effects of an orally active vasopressin V1 receptor antagonist

Clin Exp Pharmacol Physiol. 1993 May;20(5):388-91. doi: 10.1111/j.1440-1681.1993.tb01713.x.

Abstract

1. This paper reports on the in vitro and in vivo characteristics of a non-peptide vasopressin V1 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 V1 receptor antagonist radioligand, [125I]-[d(CH2)5, sarcosine7]AVP from vasopressin V1 receptors in rat liver and kidney membranes, inhibitory concentration of 50% (IC50) 4 x 10(-8), 0.3 mol/L liver and 1.5 x 10(-8), 0.2 mol/L kidney. OPC-21268 had little effect on the selective V2 antagonist radioligand [3H]desGly-NH2(9)-d(CH2)5[D-Ileu2, Ileu4]AVP binding to V2 receptors in renal membranes (IC50 > 10(-4) mol/L). 3. After oral administration to rats, OPC-21268 was an effective V1 antagonist to both liver and kidney V1 receptors, in a dose-dependent manner. 4. These studies confirm that OPC-21268 is a potent non-peptide, orally effective V1 vasopressin receptor antagonist.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Animals
  • Antidiuretic Hormone Receptor Antagonists*
  • Arginine Vasopressin / analogs & derivatives
  • Arginine Vasopressin / metabolism
  • Binding Sites
  • Dose-Response Relationship, Drug
  • Female
  • In Vitro Techniques
  • Kidney / drug effects
  • Kidney / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Piperidines / administration & dosage
  • Piperidines / pharmacology*
  • Quinolones / administration & dosage
  • Quinolones / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Vasopressin / metabolism

Substances

  • Antidiuretic Hormone Receptor Antagonists
  • Piperidines
  • Quinolones
  • Receptors, Vasopressin
  • argipressin, (1-beta-mercapto-beta,beta-cyclopentamethylenepropionic acid)-Sar(7)-
  • Arginine Vasopressin
  • OPC 21268