Noncompetitive nature of oxytocin antagonists with general structure Mpa(1)XXX(2)Sar(7)Arg(8)

Eight oxytocin (OT) antagonists with general structure Mpa(1)Sar(7)Arg(8), 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 wer...

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Bibliographic Details
Main Authors: Havass Judit
Bakos Krisztina
Márki Árpád
Gáspár Róbert
Gera Lajos
Fülöp Ferenc
Tóth Gábor
Zupkó István
Falkay György
Format: Article
Published: 2002
Series:PEPTIDES 23 No. 8
doi:10.1016/S0196-9781(02)00082-7

mtmt:1005883
Online Access:http://publicatio.bibl.u-szeged.hu/16175
Description
Summary:Eight oxytocin (OT) antagonists with general structure Mpa(1)Sar(7)Arg(8), 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 24 h 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. (C) 2002 Elsevier Science Inc. All rights reserved.
Physical Description:1419-1425
ISSN:0196-9781