Highly potent neurotensin analog that causes hypothermia and antinociception

Beth M. Tyler-Mcmahon, Jennifer A. Stewart, Fernando Farinas, Daniel J. McCormick, Elliott Richelson

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

The tridecapeptide neurotensin has long been proposed as an endogenous neuroleptic. However, for neurotensin [or neurotensin(8-13) [NT(8-13)], the active fragment] to cause its effects, it must be administered centrally. Here, we report on an analog of NT(8-13), (N-methyl-Arg),Lys,Pro,L-neo-Trp,tert-Leu,Leu (NT69L), which contains a novel amino acid, L-neo-tryptophan and exhibits high affinity for the rat and human neurotensin receptor, subtype 1. After intraperitoneal (i.p.) injection (1 mg/kg), NT69L induced hypothermia of >5°C (rectal), with a significant effect persisting for over 7 h. NT69L also caused a rapid (within 15 min) and persistent (for over 5 h) antinociceptive effect, as determined by the hot plate test. NT69L was overall the most potent and longest lasting neurotensin analog that has been reported. These studies provide the background for further testing of a stable, potent and long lasting neurotensin analog as a potential neuroleptic. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)107-111
Number of pages5
JournalEuropean Journal of Pharmacology
Volume390
Issue number1-2
DOIs
StatePublished - Feb 25 2000

Keywords

  • Hot plate test
  • NT(8-13)
  • NT69L

ASJC Scopus subject areas

  • Pharmacology

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