التفاصيل البيبلوغرافية
| العنوان: |
The cognition-enhancing activity of E1R, a novel positive allosteric modulator of sigma-1 receptors. |
| المؤلفون: |
Zvejniece, L., Vavers, E., Svalbe, B., Vilskersts, R., Domracheva, I., Vorona, M., Veinberg, G., Misane, I., Stonans, I., Kalvinsh, I., Dambrova, M. |
| المصدر: |
British Journal of Pharmacology; Feb2014, Vol. 171 Issue 3, p761-771, 11p |
| مصطلحات موضوعية: |
COGNITION, ALLOSTERIC regulation, ACETAMIDE, SIGMA-1 receptor, BINDING site assay, INTRACELLULAR calcium |
| مستخلص: |
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. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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