Characterization of the Binding of 3H‐Norzimeldine, a 5‐HT Uptake Inhibitor, to Rat Brain Homogenates
- 1 July 1984
- journal article
- research article
- Published by Wiley in Acta Pharmacologica et Toxicologica
- Vol. 55 (1) , 33-40
- https://doi.org/10.1111/j.1600-0773.1984.tb01959.x
Abstract
The binding of radiolabeled norzimeldizine, a potent selective 5-HT [5-hydroxytryptamine] reuptake inhibitor, to rat brain homogenates is described. 3H-Norzimeldine binds to a site with high affinity (KD = 10.5 nM) in a saturable manner (Bmax = 15.4 pmol/g wet weight in the cerebral cortex). The number of binding sites in the various regions of the brain parallels the capacity of the 5-HT reuptake mechanism. Drugs that inhibit the reuptake of 5-HT are also potent inhibitors of the 3H-norzimeldine binding, as are the tricyclic antidepressants, which are non-specific inhibitors of the noradrenaline [norepinephrine, NE] and the 5-HT reuptake. Lesioning experiments using DSP4 [N-(2-chloroethyl)-N-ethyl-2-bromo-benzylamine] (a NA neurotoxin) and p-chloroamphetamine (a 5-HT neurotoxin) suggest that the binding site is located on the presynaptic 5-HT nerve terminal, although a small component of the binding may be to noradrenergic uptake sites as well.Keywords
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