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?

Kód výsledku v 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>

Výsledek na webu

<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>

Jazyk výsledku

angličtina

Název v původním jazyce

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?

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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?

Popis výsledku anglicky

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.

Druh

J_x - Nezařazeno - Článek v odborném periodiku (Jimp, Jsc a Jost)

CEP obor

FH - Neurologie, neurochirurgie, neurovědy

OECD FORD obor

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Projekt

<a href="/cs/project/GAP303%2F12%2F0611" target="_blank" >GAP303/12/0611: Neurobehaviorální vyhodnocení účinnosti potenciálních léčiv Alzheimerovy choroby</a><br>

Návaznosti

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

Rok uplatnění

2016

Kód důvěrnosti údajů

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

Název periodika

Neuroscience Letters

ISSN

0304-3940

e-ISSN

—

Svazek periodika

612

Číslo periodika v rámci svazku

January

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

8

Strana od-do

261-268

Kód UT WoS článku

000369471900045

EID výsledku v databázi Scopus

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