論文

査読有り
2015年7月

SMALL CONSTRAINED SP1-7 ANALOGS BIND TO A UNIQUE SITE AND PROMOTE ANTI-ALLODYNIC EFFECTS FOLLOWING SYSTEMIC INJECTION IN MICE

NEUROSCIENCE
  • A. Jonsson
  • ,
  • R. Fransson
  • ,
  • Y. Haramaki
  • ,
  • A. Skogh
  • ,
  • E. Brolin
  • ,
  • H. Watanabe
  • ,
  • G. Nordvall
  • ,
  • M. Hallberg
  • ,
  • A. Sandstrom
  • ,
  • F. Nyberg

298
開始ページ
112
終了ページ
119
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.neuroscience.2015.04.002
出版者・発行元
PERGAMON-ELSEVIER SCIENCE LTD

Previous results have shown that the substance P (SP) N-terminal fragment SP1-7 may attenuate hyperalgesia and produce anti-allodynia in animals using various experimental models for neuropathic pain. The heptapeptide was found to induce its effects through binding to and activating specific sites apart from any known neurokinin or opioid receptor. Furthermore, we have applied a medicinal chemistry program to develop lead compounds mimicking the effect of SP1-7. The present study was designed to evaluate the pharmacological effect of these compounds using the mouse spared nerve injury (SNI) model of chronic neuropathic pain. Also, as no comprehensive screen with the aim to identify the SP1-7 target has yet been performed we screened our lead compound H-Phe-Phe-NH2 toward a panel of drug targets. The extensive target screen, including 111 targets, did not reveal any hit for the binding site among a number of known receptors or enzymes involved in pain modulation. Our animal studies confirmed that SP1-7, but also synthetic analogs thereof, possesses anti-allodynic effects in the mouse SNI model of neuropathic pain. One of the lead compounds, a constrained H-Phe-Phe-NH2 analog, was shown to exhibit a significant anti-allodynic effect. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Web of Science ® 被引用回数 : 9

リンク情報
DOI
https://doi.org/10.1016/j.neuroscience.2015.04.002
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000354783300011&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.neuroscience.2015.04.002
  • ISSN : 0306-4522
  • eISSN : 1873-7544
  • Web of Science ID : WOS:000354783300011

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