Noncompetitive nature of oxytocin antagonists with general structure Mpa1XXX2Sar7Arg8

被引：7

作者：

Havass, J

Bakos, K

Márki, A

Gáspár, R

Gera, L

Stewart, JM

Fülöp, F

Tóth, GK

Zupkó, I

Falkay, G

机构：

[1] Univ Szeged, Dept Pharmacodynam & Biopharm, H-6720 Szeged, Hungary

[2] Univ Szeged, Dept Med Chem, H-6720 Szeged, Hungary

[3] Univ Colorado, Sch Med, Dept Biochem & Mol Genet, Denver, CO 80262 USA

[4] Univ Szeged, Dept Pharmaceut Chem, H-6720 Szeged, Hungary

来源：

PEPTIDES | 2002年 / 23卷 / 08期

关键词：

oxytocin antagonist; noncompetitive; tocolysis;

D O I：

10.1016/S0196-9781(02)00082-7

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1419 / 1425

页数：7

共 22 条

[1]

Bakos K, 2001, LETT PEPT SCI, V8, P35

[2] PHARMACOLOGIC TREATMENT OF PRETERM LABOR [J].