Contribution of MATE1 to Renal Secretion of the NMDA Receptor Antagonist Memantine
Mueller F, Weitz D, Derdau V, Sandvoss M, Mertsch K, König J, Fromm M (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 14
Pages Range: 2991-2998
Journal Issue: 9
DOI: 10.1021/acs.molpharmaceut.7b00179
Abstract
The weak base memantine is actively secreted into urine, however the underlying mechanisms are insufficiently understood. Potential candidates involved in memantine renal secretion are organic cation transporter 2 (OCT2) and multidrug and toxin extrusion proteins (MATE1, MATE2-K). The aim of this in vitro study was the examination of the interaction of memantine with OCT2 and MATEs. Memantine transporter inhibition and transport were examined in HEK cells expressing human OCT2, MATE1, or MATE2-K. Monolayers of single- (MDCK-OCT2, MDCK-MATE1) and double-transfected MDCK cells (MDCK-OCT2-MATE1) were used for studies on vectorial, basal to apical memantine transport. Memantine inhibited OCT2-, MATE1-, and MATE2-K-mediated metformin transport with IC50 values of 3.2, 40.9, and 315.3 μM, respectively. In HEK cells, no relevant memantine uptake by OCT2, MATE1, or MATE2-K was detected. Vectorial transport experiments, however, indicated a role of MATE1 for memantine export: After memantine administration to the basal side of the monolayers, memantine cellular accumulation was considerably lower (MDCK-MATE1 vs MDCK control cells, P < 0.01) and memantine transcellular, basal to apical transport was higher in MATE1 expressing cells (MDCK-MATE1 vs MDCK control cells, P < 0.001 at 60 and 180 min). Both effects were abolished upon addition of the MATE inhibitor cimetidine. These experiments suggest a relevant role of MATE1 for renal secretion of memantine. In the clinical setting, renal elimination of memantine could be impaired by coadministration of MATE inhibitors.
Authors with CRIS profile
Jörg König
Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie
Martin Fromm
Lehrstuhl für Klinische Pharmakologie und Klinische Toxikologie
Involved external institutions
Germany (DE)How to cite
APA:
Mueller, F., Weitz, D., Derdau, V., Sandvoss, M., Mertsch, K., König, J., & Fromm, M. (2017). Contribution of MATE1 to Renal Secretion of the NMDA Receptor Antagonist Memantine. Molecular Pharmaceutics, 14(9), 2991-2998. https://dx.doi.org/10.1021/acs.molpharmaceut.7b00179
MLA:
Mueller, Fabian, et al. "Contribution of MATE1 to Renal Secretion of the NMDA Receptor Antagonist Memantine." Molecular Pharmaceutics 14.9 (2017): 2991-2998.
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