TY - JOUR
T1 - Selective in vivo binding of [3H]naltriben to δ-opioid receptors in mouse brain
AU - Lever, John R.
AU - Scheffel, Ursula
N1 - Funding Information:
This research was supported by NIDA grants DA 08816 and DA 08870. The authors give special thanks to Ms. Paige Finley and Ms. Sue-Ann Chapman for technical assistance, to Dr. Susan Lever for ClogP determinations, and to Drs. Rao Rapaka and Paul Hillery of the National Institute on Drug Abuse for generous gifts of various compounds.
PY - 1998/6/5
Y1 - 1998/6/5
N2 - 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.
AB - 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.
KW - Benzylidenenaltrexone
KW - Binding
KW - Brain
KW - CD1 mouse
KW - CXBK mouse
KW - In vivo
KW - Naltriben
KW - δ-Opioid receptor
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U2 - 10.1016/S0014-2999(98)00268-4
DO - 10.1016/S0014-2999(98)00268-4
M3 - Article
C2 - 9696425
AN - SCOPUS:0032486119
SN - 0014-2999
VL - 350
SP - 335
EP - 344
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
IS - 2-3
ER -