Effects of novel tacrine-related cholinesterase inhibitors in the reversal of 3-quinuclidinyl benzilate-induced cognitive deficit in rats-Is there a potential for Alzheimer's disease treatment?

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F16%3A43875549" target="_blank" >RIV/60162694:G44__/16:43875549 - isvavai.cz</a>

Result on the web

<a href="http://www.sciencedirect.com/science/article/pii/S0304394015303116" target="_blank" >http://www.sciencedirect.com/science/article/pii/S0304394015303116</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.neulet.2015.12.021" target="_blank" >10.1016/j.neulet.2015.12.021</a>

Result language

angličtina

Original language name

Effects of novel tacrine-related cholinesterase inhibitors in the reversal of 3-quinuclidinyl benzilate-induced cognitive deficit in rats-Is there a potential for Alzheimer's disease treatment?

Original language description

Inhibitors of cholinesterase are important drugs for therapy of Alzheimer's disease and the search for new modifications is extensive, including dual inhibitors or multi-target hybrid compounds. The aim of the present study was a preliminary evaluation of pro-cognitive effects of newly-developed 7-MEOTA-donepezil like hybrids (compounds no. 1 and 2) and N-alkylated tacrine derivatives (compounds no. 3 and 4) using an animal model of pharmacologically-induced cognitive deficit. Male Wistar rats were subjected to tests of learning and memory in a water maze and step-through passive avoidance task. Cognitive impairment was induced by 3-quinuclidinyl benzilate (QNB, 2 mg kg(-1)), administered intraperitoneally 1 h before training sessions. Cholinesterase inhibitors were administered as a single therapeutic dose following the QNB at 30 min at the following dose rates; 1 (25.6 mg kg(-1)), 2 (12.3 mg kg(-1)), 3 (5.7 mg kg(-1)), 4 (5.2 mg kg(-1)). The decrease in total path within the 10-swim session (water maze), the preference for target quadrant (water maze) and the entrance latency (passive avoidance) were taken as indicators of learning ability in rats. The effects of novel compounds were compared to that of standards tacrine (5.2 mg kg(-1)) and donepezil (2.65 mg kg(-1)). QNB significantly impaired spatial navigation as well as fear learning. Generally, the performance of rats was improved when treated with novel inhibitors and this effect reached efficiency of standard donepezil at selected doses. There was a significant improvement in the groups treated with compounds 2 and 3 in all behavioral tasks. The rest of the novel compounds succeed in the passive avoidance test. In summary, the potential of novel inhibitors (especially compounds 2 and 3) was proved and further detailed evaluation of these compounds as potential drugs for Alzheimer's disease treatment is proposed.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

FH - Neurology, neuro-surgery, nuero-sciences

OECD FORD branch

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Project

<a href="/en/project/GAP303%2F12%2F0611" target="_blank" >GAP303/12/0611: Neurobehavioral evaluation of potential Alzhemier`s disease drugs</a><br>

Continuities

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year

2016

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Neuroscience Letters

ISSN

0304-3940

e-ISSN

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Volume of the periodical

612

Issue of the periodical within the volume

January

Country of publishing house

IE - IRELAND

Number of pages

8

Pages from-to

261-268

UT code for WoS article

000369471900045

EID of the result in the Scopus database

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