These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The anti-aggressive drug eltoprazine preferentially binds to 5-HT1A and 5-HT1B receptor subtypes in rat brain: sensitivity to guanine nucleotides.
    Author: Sijbesma H, Schipper J, De Kloet ER.
    Journal: Eur J Pharmacol; 1990 Oct 09; 187(2):209-23. PubMed ID: 2272361.
    Abstract:
    Eltoprazine (DU 28853) inhibits offensive aggressive behaviour in several animal species. We characterized the binding of radiolabelled eltoprazine in rat brain by autoradiography. [3H]Eltoprazine displayed saturable and high-affinity binding to several brain areas, including the basal ganglia, hippocampal formation and cerebral cortex (Kd values ranging from 4.2 to 9.5 nM). The maximal binding capacities (Bmax) for [3H]eltoprazine were similar to those for [3H]5-HT and were highest in the substantia nigra and subiculum. Competition with eltoprazine for [3H]ligand binding to the various 5-HT1 receptor subtypes revealed preferential binding to 5-HT1A (IC50 values ranging from 42 to 50 nM) and 5-HT1B (IC50 values ranging from 25 to 38 nM) recognition sites. The drug had moderate affinity for 5-HT1C sites (IC50 = 282 nM). Addition of GTP or its stable analogue Gpp(NH)p to the radioligand assay caused a marked reduction (50-90%) in both [3H]eltoprazine and [3H]5-HT binding. These effects were substantially less in the choroid plexus. The binding of the antagonist (-)[125I]Iodocyanopindolol ([125I]ICYP) to 5-HT1B recognition sites, as quantified in the subiculum and substantia nigra, was either unaltered or slightly enhanced by the addition of 10(-3) M GTP. Furthermore, GTP did not affect the competition for [125I]ICYP binding by the 5-HT1-antagonist methiothepin, whereas it did significantly reduce the displacement by eltoprazine, resulting in an almost twofold increase in IC50 values. The data indicate that the anti-aggressive drug eltoprazine preferentially binds to 5-HT1A and 5-HT1B receptor sites and that this interaction is modulated by guanine nucleotides.
    [Abstract] [Full Text] [Related] [New Search]