Interaction of Afobazole with σ1-Receptors

  title={Interaction of Afobazole with $\sigma$1-Receptors},
  author={Sergey B. Seredenin and Tatiana A. Antipova and Mikhail V. Voronin and Svetlana Yu Kurchashova and Alexander N. Kuimov},
  journal={Bulletin of Experimental Biology and Medicine},
In vitro radioligand assay revealed interaction of afobazole with σ1-receptors (Ki=5.9 × 10—6 M). Translocation of σ1-receptors from the endoplasmic reticulum to the outer membrane was demonstrated by confocal microscopy. Experiments were performed on the model of HT-22 immortalized hippocampal cells after incubation with afobazole in a concentration of 10—8 M. 
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Data indicate that afobazole inhibits microglial response to P2Y and P2X purinergic receptor activation by functioning as a pan-selective σ-receptor agonist and provides cytoprotection during and after ischemia.
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Analysis of Cytoprotective Properties of Afobazole in Streptozotocin Model of Diabetes.
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Involvement of Chaperone Sigma1R in the Anxiolytic Effect of Fabomotizole
Results of initial in silico study showed that fabomotizole locates in the active center of Sigma1R, reproducing the interactions with the site’s amino acids common for established Sigma 1R ligands, with the ΔGbind value closer to that of agonist (+)-pentazocine in the 6DK1 binding site.
Bi-phasic dose response in the preclinical and clinical developments of sigma-1 receptor ligands for the treatment of neurodegenerative disorders
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    Expert opinion on drug discovery
  • 2020
The data showing the high therapeutic potential of S1R drugs for the treatment of neurodegenerative diseases are presented, focusing on pridopidine as a potent and selective S 1R agonist under clinical development.


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The results indicate that σ-1 receptors localize on ER-LDs and upon stimulation translocate on continuous endoplasmic reticulum reticular network toward peripheries of cells, and suggest that ρ-1 receptor' dynamic translocation might affect lipid transport and distribution in neuronal cells.
An update on the development of drugs for neuropsychiatric disorders: focusing on the σ1 receptor ligand
Primary clinical targets of σ1 receptor ligands are proposed to include stroke, neurodegenerative disorders and depression, and ligands for the ρ1 receptor may constitute a new class of therapeutic drugs targeting an endoplasmic reticular protein.
Ligand-dependent localization and intracellular stability of sigma-1 receptors in CHO-K1 cells
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Molecular and ligand-binding characterization of the sigma-receptor in the Jurkat human T lymphocyte cell line.
Northern analysis and reverse transcription-polymerase chain reaction provided evidence for the expression of the recently cloned type 1 sigma-receptor (sigma-R1) in Jurkat cells and the binding of [3H]progesterone, a putative endogenous ligand to sigma, could be directly demonstrated by using heterologously expressed sigma -R1 cDNA.
σ-1 Receptors (σ1 Binding Sites) Form Raft-Like Microdomains and Target Lipid Droplets on the Endoplasmic Reticulum: Roles in Endoplasmic Reticulum Lipid Compartmentalization and Export
It is found that σ-1 receptors specifically target lipid storage sites (lipid droplets) on the endoplasmic reticulum by forming a distinct class of lipid microdomains in NG108-15 cells.
Intracellular sigma1 receptor modulates phospholipase C and protein kinase C activities in the brainstem.
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