In vitro pharmacological profile of a novel structural class of oxytocin antagonists

J Pharmacol Exp Ther. 1991 Jan;256(1):304-8.


A number of structurally novel cyclic hexapeptides have been characterized as potent and selective oxytocin (OT) antagonists in vitro. As a representative of this class of compounds, L-366,948 [[cyclo(L-prolyl-D-2-naphthylalanyl-L-isoleucyl-D-pipecolyl- L-pipecolyl-D- histidyl)]] exhibited a high binding affinity (Ki, low nanomolar) for OT receptors in rat (uterus and mammary) and primate (pregnant rhesus and human myometrium) tissue with a several hundred-fold binding selectivity vs. rat arginine vasopressin (AVP)-V1 (liver) and AVP-V2 (kidney medulla) receptors. In functional assays, L-366,948 was a pure OT antagonist, blocking both OT-stimulated contraction of the isolated rat uterus (pA2, 8.5) and phosphatidylinositol turnover in uterine slices (IC50, 40 vs. 3 nM OT), with no evidence of partial agonist activity. L-366,948 was comparatively weak as an antagonist of AVP-induced contraction of the isolated rat tail artery (AVP-V1 receptor) and AVP-stimulated adenylate cyclase (AVP-V2 receptor) activity in rat kidney medulla and did not influence prostaglandin F2 alpha- or bradykinin-induced contractions of the isolated rat uterus. L-366,948 and related compounds described in this report represent new experimental tools for the study of the pharmacology and physiology of OT.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Arginine Vasopressin / antagonists & inhibitors
  • Female
  • Kinetics
  • Male
  • Molecular Sequence Data
  • Oxytocin / antagonists & inhibitors*
  • Peptides, Cyclic / metabolism
  • Peptides, Cyclic / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Tritium
  • Uterus / anatomy & histology
  • Uterus / drug effects


  • Peptides, Cyclic
  • Tritium
  • Arginine Vasopressin
  • L 365209
  • L 366682
  • L 366948
  • Oxytocin