Selective in vivo binding of [3H]naltriben to delta-opioid receptors in mouse brain.
Naltriben (NTB) is a selective antagonist for the putative delta2-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 cerebellum. Robust rank order correlation was found between [3H]naltriben uptake in discrete brain regions and prior delta-opioid receptor binding determinations in vitro and in vivo. [3H]Naltriben binding in vivo was saturable, and was blocked by the delta-opioid receptor antagonist naltrindole, but not by the mu-opioid receptor antagonist cyprodime or the K-opioid receptor agonist (trans)-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]ben zeneacetamide mesylate (U50,488H). (E)-7-Benzylidenenaltrexone (BNTX), a selective antagonist for the putative delta1-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 delta2-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 delta1- but not delta2-opioid receptor agonist effects, was quite similar to that found for CD1 mice.
Lever
J R
JR
Department of Environmental Health Sciences, The Johns Hopkins University School of Hygiene and Public Health, Baltimore, MD 21205, USA. jlever@welchlink.welch.jhu.edu
Scheffel
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D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001921:Brain / Q000378:metabolism*; D007275:Injections, Intravenous; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000493:pharmacokinetics* / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism*
D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran; D009271:Naltrexone