Oxytocin and vasopressin agonists and antagonists as research tools and potential therapeutics

J Neuroendocrinol. 2012 Apr;24(4):609-28. doi: 10.1111/j.1365-2826.2012.02303.x.


We recently reviewed the status of peptide and nonpeptide agonists and antagonists for the V(1a), V(1b) and V(2) receptors for arginine vasopressin (AVP) and the oxytocin receptor for oxytocin (OT). In the present review, we update the status of peptides and nonpeptides as: (i) research tools and (ii) therapeutic agents. We also present our recent findings on the design of fluorescent ligands for V(1b) receptor localisation and for OT receptor dimerisation. We note the exciting discoveries regarding two novel naturally occurring analogues of OT. Recent reports of a selective VP V(1a) agonist and a selective OT agonist point to the continued therapeutic potential of peptides in this field. To date, only two nonpeptides, the V(2) /V(1a) antagonist, conivaptan and the V(2) antagonist tolvaptan have received Food and Drug Administration approval for clinical use. The development of nonpeptide AVP V(1a), V(1b) and V(2) antagonists and OT agonists and antagonists has recently been abandoned by Merck, Sanofi and Pfizer. A promising OT antagonist, Retosiban, developed at Glaxo SmithKline is currently in a Phase II clinical trial for the prevention of premature labour. A number of the nonpeptide ligands that were not successful in clinical trials are proving to be valuable as research tools. Peptide agonists and antagonists continue to be very widely used as research tools in this field. In this regard, we present receptor data on some of the most widely used peptide and nonpeptide ligands, as a guide for their use, especially with regard to receptor selectivity and species differences.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antidiuretic Hormone Receptor Antagonists
  • Arginine Vasopressin / agonists
  • Arginine Vasopressin / analogs & derivatives*
  • Arginine Vasopressin / antagonists & inhibitors
  • Arginine Vasopressin / therapeutic use*
  • Clinical Trials as Topic
  • Drug Evaluation, Preclinical / methods
  • Drug Evaluation, Preclinical / statistics & numerical data
  • Humans
  • Oxytocin / agonists
  • Oxytocin / analogs & derivatives*
  • Oxytocin / antagonists & inhibitors
  • Oxytocin / therapeutic use*
  • Receptors, Oxytocin / agonists
  • Receptors, Oxytocin / antagonists & inhibitors
  • Receptors, Vasopressin / agonists
  • Structure-Activity Relationship


  • Antidiuretic Hormone Receptor Antagonists
  • Receptors, Oxytocin
  • Receptors, Vasopressin
  • Arginine Vasopressin
  • Oxytocin