A nonpeptide oxytocin receptor antagonist radioligand highly selective for human receptors

Eur J Pharmacol. 2002 Aug 16;450(1):19-28. doi: 10.1016/s0014-2999(02)02048-4.

Abstract

A novel, potent nonpeptide oxytocin receptor antagonist (1-(1-(2-(2,2,2-trifluoroethoxy)-4-(1-methylsulfonyl-4-piperidinyloxy) phenylacetyl)-4-piperidinyl)-3,4-dihydro-2(1H)-quinolinone) has been identified that can be labeled to high specific activity with [35S]. In binding studies, this compound exhibits sub-nanomolar affinity and a high degree of selectivity (900-1800-fold) for human oxytocin receptors compared to human vasopressin receptors. This compound appears suitable for studying the pharmacology of oxytocin receptors in human and nonhuman primate tissues, for which there is currently a paucity of highly selective tools. It may also be useful as a nonlabeled competitor or as a radioligand in autoradiographic studies of oxytocin receptor localization in these tissues.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Antidiuretic Hormone Receptor Antagonists
  • Binding Sites
  • Binding, Competitive
  • Blood Platelets / metabolism
  • CHO Cells
  • Calcium / metabolism
  • Cricetinae
  • Humans
  • In Vitro Techniques
  • Kinetics
  • Ligands
  • Piperidines / chemical synthesis
  • Piperidines / pharmacology*
  • Quinolones / chemical synthesis
  • Quinolones / pharmacology*
  • Radioligand Assay
  • Receptors, Oxytocin / antagonists & inhibitors*
  • Receptors, Oxytocin / metabolism*
  • Receptors, Vasopressin / metabolism*

Substances

  • 1-(1-(2-(2,2,2-trifluoroethoxy)-4-(1-methylsulfonyl-4-piperidinyloxy) phenylacetyl)-4-piperidinyl)-3,4-dihydro-2(1H)-quinolinone
  • Antidiuretic Hormone Receptor Antagonists
  • Ligands
  • Piperidines
  • Quinolones
  • Receptors, Oxytocin
  • Receptors, Vasopressin
  • Calcium