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

Naltriben (NTB) is a selective antagonist for the putative delta(2)-opioid receptor. We have determined the regional kinetics and pharmacological profile of [H-3]naltriben in vivo in mouse brain. After i.v. administration to CD1 mice, [H-3]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 [H-3]naltriben uptake in discrete brain regions and prior delta-opioid receptor binding determinations in vitro and in vivo. [H-3]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 kappa-opioid receptor agonist (trans)-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]benzeneacetamide mesylate (U50,488H). (E)-7-Benzylidenenaltrexone (BNTX), a selective antagonist for the putative delta(1)-opioid receptor, was 9.6- to 12.9-fold less potent than naltriben as an inhibitor of [H-3]naltriben binding. Thus, the sites labeled by [H-3]naltriben in vivo may correspond to the delta(2)-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 [H-3]naltriben in brains from CXB-7/BY (CXBK) mice, a strain that shows supraspinal delta(1)- but not delta(2)-opioid receptor agonist effects, was quite similar to that found for CD1 mice. (C) 1998 Elsevier Science B.V. All rights reserved.