Please use this identifier to cite or link to this item:
10.1111/bph.12506
Title: | The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors |
Authors: | Zvejniece, L. Vavers, E. Svalbe, B. Vilskersts, R. Domracheva, I. Vorona, M. Veinberg, G. Misane, I. Stonans, I. Kalvinsh, I. Dambrova, M. Rīga Stradiņš University |
Keywords: | behaviour;CNS drugs;cognition;E1R;neurodegenerative diseases;racetam;receptor binding;scopolamine;sigma-1 receptor;3.1 Basic medicine;1.1. Scientific article indexed in Web of Science and/or Scopus database;Pharmacology |
Issue Date: | Feb-2014 |
Citation: | Zvejniece , L , Vavers , E , Svalbe , B , Vilskersts , R , Domracheva , I , Vorona , M , Veinberg , G , Misane , I , Stonans , I , Kalvinsh , I & Dambrova , M 2014 , ' The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors ' , British Journal of Pharmacology , vol. 171 , no. 3 , pp. 761-771 . https://doi.org/10.1111/bph.12506 |
Abstract: | Background and Purpose Here, we describe the in vitro and in vivo effects of (4R,5S)-2-(5-methyl-2-oxo-4-phenyl-pyrrolidin-1-yl)-acetamide (E1R), a novel positive allosteric modulator of sigma-1 receptors. Experimental Approach E1R was tested for sigma receptor binding activity in a [3H](+)- pentazocine assay, in bradykinin (BK)-induced intracellular Ca2+ concentration ([Ca2+]i) assays and in an electrically stimulated rat vas deferens model. E1R's effects on cognitive function were tested using passive avoidance (PA) and Y-maze tests in mice. A selective sigma-1 receptor antagonist (NE-100), was used to study the involvement of the sigma-1 receptor in the effects of E1R. The open-field test was used to detect the effects of E1R on locomotion. Key Results Pretreatment with E1R enhanced the selective sigma-1 receptor agonist PRE-084's stimulating effect during a model study employing electrically stimulated rat vasa deferentia and an assay measuring the BK-induced [Ca2+]i increase. Pretreatment with E1R facilitated PA retention in a dose-related manner. Furthermore, E1R alleviated the scopolamine-induced cognitive impairment during the PA and Y-maze tests in mice. The in vivo and in vitro effects of E1R were blocked by treatment with the selective sigma-1 receptor antagonist NE-100. E1R did not affect locomotor activity. Conclusion and Implications E1R is a novel 4,5-disubstituted derivative of piracetam that enhances cognition and demonstrates efficacy against scopolamine-induced cholinergic dysfunction in mice. These effects are attributed to its positive modulatory action on the sigma-1 receptor and this activity may be relevant when developing new drugs for treating cognitive symptoms related to neurodegenerative diseases. |
DOI: | 10.1111/bph.12506 |
ISSN: | 0007-1188 |
Appears in Collections: | Research outputs from Pure / Zinātniskās darbības rezultāti no ZDIS Pure |
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The_cognition_enhancing.pdf | 1.03 MB | Adobe PDF | View/Open |
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