Comparison of (R)-[3H]tomoxetine and (R/S)-[3H]nisoxetine binding in rat brain.

Abstract:

:(R)-[3H]Tomoxetine is a radioligand that binds to the norepinephrine (NE) uptake site with high affinity but also binds to a second, lower-affinity site. The goal of the present study was to identify the nature of this low-affinity site by comparing the binding properties of (R)-[3H]tomoxetine with those of (R/S)-[3H]nisoxetine, a highly selective ligand for the NE uptake site. In homogenate binding studies, both radioligands bound to the NE uptake site with high affinity, whereas (R)-[3H]tomoxetine also bound to a second, lower-affinity site. The autoradiographic distribution of binding sites for both radioligands is consistent with the known distribution of NE-containing neurons. However, low levels of (R)-[3H]tomoxetine binding were seen in the caudate-putamen, globus pallidus, olfactory tubercle, and zona reticulata of the substantia nigra, where (R/S)-[3H]nisoxetine binding was almost absent. In homogenates of the caudate-putamen, the NE uptake inhibitors desipramine and (R)-nisoxetine and the serotonin (5-HT) uptake inhibitor citalopram produced biphasic displacement curves. Autoradiographic studies using 10 nM (R)-nisoxetine to mask the binding of (R)-[3H]tomoxetine to the NE uptake site produced autoradiograms that were similar to those produced by [3H]citalopram. Therefore, (R)-[3H]tomoxetine binds to the NE uptake site with high affinity and the 5-HT uptake site with somewhat lower affinity.

journal_name

J Neurochem

authors

Gehlert DR,Schober DA,Gackenheimer SL

doi

10.1046/j.1471-4159.1995.64062792.x

subject

Has Abstract

pub_date

1995-06-01 00:00:00

pages

2792-800

issue

6

eissn

0022-3042

issn

1471-4159

journal_volume

64

pub_type

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