[3H]nisoxetine--a radioligand for noradrenaline reuptake sites: correlation with inhibition of [3H]noradrenaline uptake and effect of DSP-4 lesioning and antidepressant treatments.

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Cheetham SC, Viggers JA, Butler SA, Prow MR, Heal DJ

[3H]nisoxetine--a radioligand for noradrenaline reuptake sites: correlation with inhibition of [3H]noradrenaline uptake and effect of DSP-4 lesioning and antidepressant treatments.

Neuropharmacology. 1996 Jan;35(1):63-70.

PubMed ID

8684598 [ View in PubMed

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Abstract

Nisoxetine is a potent and selective inhibitor of noradrenaline uptake into noradrenergic neurones. [3H]Nisoxetine binding to rat frontal cortical membranes was of high affinity. The binding data of both competition and saturation studies fitted a single site binding model. [3H]Nisoxetine binding was potently inhibited by the selective noradrenaline uptake inhibitors desipramine and protriptyline. In addition, a very good correlation was obtained between the ability of 25 monoamine reuptake inhibitors and related compounds both to inhibit [3H]nisoxetine binding and to inhibit [3H]noradrenaline uptake in rat frontal cortex. DSP-4 (10-100 mg/kg, i.p.) dose-dependently depleted cortical noradrenaline concentrations (51-100%), with no significant effects on 5-HT and dopamine. These depletions, which were used as a marker of loss of noradrenergic nerve terminals, were associated with a dose-dependent decrease in the number of [3H]nisoxetine binding sites (20-97%) with no change in binding affinity. Furthermore, a good correlation was obtained between cortical noradrenaline concentrations and the number of [3H]nisoxetine binding sites. These data support the view that [3H]nisoxetine binds to a single population of homogeneous sites associated with the noradrenaline transporter complex. Using this ligand, the effects of repeated administration of both antidepressant drugs with a range of pharmacological actions and of electroconvulsive shock on noradrenaline reuptake sites were examined. The number and affinity of [3H]nisoxetine binding sites were unaltered by all treatments. It is unlikely, therefore, that antidepressant therapy would produce adaptive changes in noradrenaline uptake sites.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Protriptyline	Sodium-dependent noradrenaline transporter	Protein	Humans	Yes	Inhibitor	Details