Noncompetitive nature of oxytocin antagonists with general structure Mpa1Xxx2Sar7Arg8

J. Havass, K. Bakos, Á Márki, R. Gáspár, L. Gera, J. M. Stewart, F. Fülöp, G. K. Tóth, I. Zupkó, G. Falkay

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9 Citations (Scopus)

Abstract

Eight oxytocin (OT) antagonists with general structure Mpa1Sar7Arg8, substituted at position 2 with conformationally constrained and bulky amino acids, were synthesized and pharmacologically tested. Binding affinities and selectivities of compounds for OT, and vasopressin receptor subtypes were investigated. In vitro effects of antagonists were evaluated via inhibition of OT-induced contractions of isolated guinea-pig uterus. The abilities of OT antagonists to inhibit spontaneous contractility in 24h postpartum rat uterus were investigated. These peptides exhibited pseudoirreversible pharmacological properties, and comprise a novel group of OT antagonists for potential clinical use. Their noncompetitive pharmacological nature can be of therapeutic benefit through a sustained effect on myometrium.

Original languageEnglish
Pages (from-to)1419-1425
Number of pages7
JournalPeptides
Volume23
Issue number8
DOIs
Publication statusPublished - Aug 1 2002

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Keywords

  • Noncompetitive
  • Oxytocin antagonist
  • Tocolysis

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Endocrinology
  • Cellular and Molecular Neuroscience

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