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@article{1807994,
author = {Valis, M. and Herman, D. and Vanova, N. and Masopust, J. and Vysata, O. and Hort, J. and Pavelek, Z. and Klimova, B. and Kuca, K. and Misik, J. and Karasova, J. Z.},
article_location = {Lausanne},
doi = {http://dx.doi.org/10.3389/fphar.2019.00943},
keywords = {memantine; Alzheimer's disease; clinical study; cerebrospinal fluid concentrations; oxidative stress; biomarkers},
language = {eng},
issn = {1663-9812},
journal = {Frontiers in Pharmacology},
note = {RIV/00159816:_____/19:00072496},
title = {The Concentration of Memantine in the Cerebrospinal Fluid of Alzheimer's Disease Patients and Its Consequence to Oxidative Stress Biomarkers},
url = {https://www.frontiersin.org/articles/10.3389/fphar.2019.00943/full},
volume = {10},
year = {2019}
}
TY - JOUR
ID - 1807994
AU - Valis, M. - Herman, D. - Vanova, N. - Masopust, J. - Vysata, O. - Hort, J. - Pavelek, Z. - Klimova, B. - Kuca, K. - Misik, J. - Karasova, J. Z.
PY - 2019
TI - The Concentration of Memantine in the Cerebrospinal Fluid of Alzheimer's Disease Patients and Its Consequence to Oxidative Stress Biomarkers
JF - Frontiers in Pharmacology
VL - 10
PB - Frontiers Media SA
SN - 16639812
N1 - RIV/00159816:_____/19:00072496
KW - memantine
KW - Alzheimer's disease
KW - clinical study
KW - cerebrospinal fluid concentrations
KW - oxidative stress
KW - biomarkers
UR - https://www.frontiersin.org/articles/10.3389/fphar.2019.00943/full
N2 - Memantine is a noncompetitive 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/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 h 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/cerebrospinal fluid (CSF) ratio for all time intervals were within the range of 45.89% (6 h) to 55.60% (18 h), 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 112ng/ml (GluN2C), and this value was achieved only in three cases. The memantine cerebrospinal fluid concentration did not reach one quarter of the IC50 value in five 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.
ER -
VALIS, M., D. HERMAN, N. VANOVA, J. MASOPUST, O. VYSATA, J. HORT, Z. PAVELEK, B. KLIMOVA, K. KUCA, J. MISIK and J. Z. KARASOVA. The Concentration of Memantine in the Cerebrospinal Fluid of Alzheimer's Disease Patients and Its Consequence to Oxidative Stress Biomarkers. \textit{Frontiers in Pharmacology}. Lausanne: Frontiers Media SA, 2019, vol.~10, 8 pp. ISSN~1663-9812. Available from: https://dx.doi.org/10.3389/fphar.2019.00943.
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