Number of the records: 1
The pharmacology of tacrine at N-methyl-D-aspartate receptors
- 1.
SYSNO ASEP 0474134 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title The pharmacology of tacrine at N-methyl-D-aspartate receptors Author(s) Horák, Martin (FGU-C) RID, ORCID
Holubová, K. (CZ)
Nepovímová, E. (CZ)
Krůšek, Jan (FGU-C) RID, ORCID
Kaniaková, Martina (FGU-C) RID, ORCID
Korábečný, J. (CZ)
Vyklický ml., Ladislav (FGU-C) RID, ORCID, SAI
Kuča, K. (CZ)
Stuchlík, Aleš (FGU-C) RID, ORCID
Říčný, J. (CZ)
Valeš, K. (CZ)
Soukup, O. (CZ)Source Title Progress in Neuro-Psychopharmacology & Biological Psychiatry. - : Elsevier - ISSN 0278-5846
Roč. 75, Apr 3 (2017), s. 54-62Number of pages 9 s. Language eng - English Country US - United States Keywords tacrine ; NMDA receptors ; long term potentiation ; cognition ; M1 activation ; multi-target directed ligands Subject RIV FH - Neurology OECD category Neurosciences (including psychophysiology R&D Projects GA16-08554S GA ČR - Czech Science Foundation (CSF) Institutional support FGU-C - RVO:67985823 UT WOS 000396947700007 EID SCOPUS 85009749026 DOI 10.1016/j.pnpbp.2017.01.003 Annotation 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'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 M1 receptor activation, which leads to inhibition of Ca2 +-activated potassium channels. Such inhibition prevents membrane repolarization 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. Workplace Institute of Physiology Contact Lucie Trajhanová, lucie.trajhanova@fgu.cas.cz, Tel.: 241 062 400 Year of Publishing 2018
Number of the records: 1