The pharmacology of tacrine at N-methyl-D-aspartate receptors

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00179906%3A_____%2F17%3A10359014" target="_blank" >RIV/00179906:_____/17:10359014 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/67985823:_____/17:00474134 RIV/00023752:_____/17:43915349

Výsledek na webu

<a href="http://dx.doi.org/10.1016/j.pnpbp.2017.01.003" target="_blank" >http://dx.doi.org/10.1016/j.pnpbp.2017.01.003</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.pnpbp.2017.01.003" target="_blank" >10.1016/j.pnpbp.2017.01.003</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The pharmacology of tacrine at N-methyl-D-aspartate receptors

Popis výsledku v původním jazyce

The mechanism of tacrine as a precognitive drug has been considered to be complex and not fully understood. It has been reported to involve a wide spectrum of targets involving cholinergic, gabaergic, nitrinergic and glutamatergic pathways. Here, we review the effect of tacrine and its derivatives on the NMDA receptors (NMDAR) with a focus on the mechanism of action and biological consequences related to the Alzheimer&apos;s disease treatment. Our findings indicate that effect of tacrine on glutamatergic neurons is both direct and indirect. Direct NMDAR antagonistic effect is often reported by in vitro studies; however, it is achieved by high tacrine concentrations which are not likely to occur under clinical conditions. The impact on memory and behavioral testing can be ascribed to indirect effects of tacrine caused by influencing the NMDAR-mediated currents via Ml receptor activation, which leads to inhibition of Ca2+-activated potassium channels. Such inhibition prevents membrane re polarization leading to prolonged NMDAR activation and subsequently to long term potentiation. Considering these findings, we can conclude that tacrine-derivatives with dual cholinesterase and NMDARs modulating activity may represent a promising approach in the drug development for diseases associated with cognitive dysfunction, such as the Alzheimer disease.

Název v anglickém jazyce

The pharmacology of tacrine at N-methyl-D-aspartate receptors

Popis výsledku anglicky

The mechanism of tacrine as a precognitive drug has been considered to be complex and not fully understood. It has been reported to involve a wide spectrum of targets involving cholinergic, gabaergic, nitrinergic and glutamatergic pathways. Here, we review the effect of tacrine and its derivatives on the NMDA receptors (NMDAR) with a focus on the mechanism of action and biological consequences related to the Alzheimer&apos;s disease treatment. Our findings indicate that effect of tacrine on glutamatergic neurons is both direct and indirect. Direct NMDAR antagonistic effect is often reported by in vitro studies; however, it is achieved by high tacrine concentrations which are not likely to occur under clinical conditions. The impact on memory and behavioral testing can be ascribed to indirect effects of tacrine caused by influencing the NMDAR-mediated currents via Ml receptor activation, which leads to inhibition of Ca2+-activated potassium channels. Such inhibition prevents membrane re polarization leading to prolonged NMDAR activation and subsequently to long term potentiation. Considering these findings, we can conclude that tacrine-derivatives with dual cholinesterase and NMDARs modulating activity may represent a promising approach in the drug development for diseases associated with cognitive dysfunction, such as the Alzheimer disease.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

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

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Progress in Neuro-Psychopharmacology &amp; Biological Psychiatry

ISSN

0278-5846

e-ISSN

—

Svazek periodika

75

Číslo periodika v rámci svazku

April

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

9

Strana od-do

54-62

Kód UT WoS článku

000396947700007

EID výsledku v databázi Scopus

2-s2.0-85009749026