Selective in vivo binding of [3H]naltriben to δ-opioid receptors in mouse brain

John R. Lever, Ursula Scheffel

Research output: Contribution to journalArticle

Abstract

Naltriben (NTB) is a selective antagonist for the putative δ2-opioid receptor. We have determined the regional kinetics and pharmacological profile of [3H]naltriben in vivo in mouse brain. After i.v. administration to CD1 mice, [3H]naltriben uptake and retention were high in striatum, cortical regions and olfactory tubercles, and low in superior colliculi and cerebellu. Robust rank order correlation was found between [3H]naltriben uptake in discrete brain regions and prior δ-opioid receptor binding determinations in vitro and in vivo [3H]Naltriben binding in vivo was saturable, and was blocked by the δ-opioid receptor antagonist naltrindole, but not by the μ-opioid receptor antagonist cyprodime or the κ-opioid receptor agonist (trans)-(±)-3,4-dicholoro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide mesylate (U50, 488H). (E)-7- Benzylidenenaltrexone (BNTX), a selective antagonist for the putative δ1- opioid receptor, was 9.6- to 12.9-fold less potent than naltriben as an inhibitor of [3H]naltriben binding. Thus, the sites labeled by [3H]naltriben in vivo may correspond to the δ2-opioid receptor subtype. Such assignment is not definitive, particularly considering the 4-fold higher brain uptake of naltriben as compared to (E)-7-benzylidenenaltrexone. Moreover, the regional distribution of [3H]naltriben in brains from CXB- 7/BY (CXBK) mice, a strain that shows supraspinal δ1- but not δ2-opioid receptor agonist effects, was quite similar to that found for CD1 mice.

Original languageEnglish (US)
Pages (from-to)335-344
Number of pages10
JournalEuropean Journal of Pharmacology
Volume350
Issue number2-3
DOIs
StatePublished - Jun 5 1998

Keywords

  • Benzylidenenaltrexone
  • Binding
  • Brain
  • CD1 mouse
  • CXBK mouse
  • In vivo
  • Naltriben
  • δ-Opioid receptor

ASJC Scopus subject areas

  • Pharmacology

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