Characterization of the binding of 3H-norzimeldine, a 5-HT uptake inhibitor, to rat brain homogenates.
The binding of radiolabelled norzimeldine, a potent selective 5-HT 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 and the 5-HT reuptake. Lesioning experiments using DSP4 (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.
D000818:Animals; D000928:Antidepressive Agents / Q000378:metabolism* / Q000494:pharmacology; D001665:Binding Sites; D001921:Brain / Q000378:metabolism*; D007099:Imipramine / Q000378:metabolism; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D014316:Tritium; D015031:Zimeldine / Q000031:analogs & derivatives* / Q000378:metabolism; D010133:p-Chloroamphetamine / Q000494:pharmacology
D000928:Antidepressive Agents; D011985:Receptors, Serotonin; D014316:Tritium; D012701:Serotonin; D015031:Zimeldine; C017578:norzimelidine; D010133:p-Chloroamphetamine; D007099:Imipramine