The concentration of memantine in the cerebrospinal fluid of Alzheimer´s disease patients and its consequence to oxidative stress biomarkers

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60162694%3AG44__%2F19%3A00537046" target="_blank" >RIV/60162694:G44__/19:00537046 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00179906:_____/19:10398436 RIV/00216208:11130/19:10398436 RIV/00216208:11150/19:10398436 RIV/00216208:11160/19:10398436 a 2 dalších

Výsledek na webu

<a href="https://www.frontiersin.org/articles/10.3389/fphar.2019.00943/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fphar.2019.00943/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphar.2019.00943" target="_blank" >10.3389/fphar.2019.00943</a>

Jazyk výsledku

angličtina

Název v původním jazyce

The concentration of memantine in the cerebrospinal fluid of Alzheimer´s disease patients and its consequence to oxidative stress biomarkers

Popis výsledku v původním jazyce

Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist utilized as a palliative cure for Alzheimer's disease. This is the second study examining the memantine concentrations in cerebrospinal fluid. The previously published study enrolled six patients and three of them were theoretically in a steady state. In our study, we enrolled 22 patients who regularly used a standard therapeutic dose of memantine (20 mg per day, oral administration) before the sample collection. Patients were divided into four groups, according to the time of plasma and cerebrospinal fluid collection: 6, 12, 18 and 24 hours after memantine administration. The cerebrospinal fluid samples were also assessed for selected oxidative stress parameters (malondialdehyde, 3-nitrotyrosine, glutathione, non-protein thiols and non-protein disulfides). The plasma/CSF ratio for all time intervals were within the range of 45.89 % (6 hours) - 55.60 % (18 hours), which corresponds with previously published findings in most patients. The other aim of our study was to deduce whether the achieved “real” memantine concentration in the central compartment was sufficient to block NMDA receptors. The IC50 value of memantine as an NMDA antagonist is in micromolar range; the lowest limit is 112 ng/mL (GluN2C), and this value was achieved only in three cases. The memantine cerebrospinal fluid concentration did not reach ¼ of the IC50 value in 5 cases (one patient was excluded for noncompliance); therefore, the potency of memantine as a therapeutic effect in patients may be questionable. However, it appears that memantine therapy positively affected the levels of some oxidative stress parameters, especially non-protein thiols and 3-nitrotyrosine. © 2019 Frontiers Media S.A.. All rights reserved.

Název v anglickém jazyce

The concentration of memantine in the cerebrospinal fluid of Alzheimer´s disease patients and its consequence to oxidative stress biomarkers

Popis výsledku anglicky

Memantine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist utilized as a palliative cure for Alzheimer's disease. This is the second study examining the memantine concentrations in cerebrospinal fluid. The previously published study enrolled six patients and three of them were theoretically in a steady state. In our study, we enrolled 22 patients who regularly used a standard therapeutic dose of memantine (20 mg per day, oral administration) before the sample collection. Patients were divided into four groups, according to the time of plasma and cerebrospinal fluid collection: 6, 12, 18 and 24 hours after memantine administration. The cerebrospinal fluid samples were also assessed for selected oxidative stress parameters (malondialdehyde, 3-nitrotyrosine, glutathione, non-protein thiols and non-protein disulfides). The plasma/CSF ratio for all time intervals were within the range of 45.89 % (6 hours) - 55.60 % (18 hours), which corresponds with previously published findings in most patients. The other aim of our study was to deduce whether the achieved “real” memantine concentration in the central compartment was sufficient to block NMDA receptors. The IC50 value of memantine as an NMDA antagonist is in micromolar range; the lowest limit is 112 ng/mL (GluN2C), and this value was achieved only in three cases. The memantine cerebrospinal fluid concentration did not reach ¼ of the IC50 value in 5 cases (one patient was excluded for noncompliance); therefore, the potency of memantine as a therapeutic effect in patients may be questionable. However, it appears that memantine therapy positively affected the levels of some oxidative stress parameters, especially non-protein thiols and 3-nitrotyrosine. © 2019 Frontiers Media S.A.. All rights reserved.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30104 - Pharmacology and pharmacy

Projekt

<a href="/cs/project/EF18_069%2F0010054" target="_blank" >EF18_069/0010054: IT4Neuro(degeneration)</a><br>

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Frontiers in Pharmacology

ISSN

1663-9812

e-ISSN

1663-9812

Svazek periodika

10

Číslo periodika v rámci svazku

Aug

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

8

Strana od-do

943

Kód UT WoS článku

000482910900001

EID výsledku v databázi Scopus

2-s2.0-85070694221