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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/26290

Title: Brivaracetam does not modulate ionotropic channels activated by glutamate, gamma-aminobutyric acid, and glycine in hippocampal neurons
Authors: Niespodziany, Isabelle
Rigo, Jean-Michel
Moonen, Gustave
Matagne, Alain
Klitgaard, Henrik
Wolff, Christian
Issue Date: 2017
Publisher: WILEY
Citation: EPILEPSIA, 58(11), p. E157-E161
Abstract: Brivaracetam (BRV) is a selective, high-affinity ligand for synaptic vesicle protein 2A (SV2A), recently approved as adjunctive treatment for drug-refractory partial-onset seizures in adults. BRV binds SV2A with higher affinity than levetiracetam (LEV), and was shown to have a differential interaction with SV2A. Because LEV was reported to interact with multiple excitatory and inhibitory ligand-gated ion channels and that may impact its pharmacological profile, we were interested in determining whether BRV directly modulates inhibitory and excitatory ionotropic receptors in central neurons. Voltage-clamp experiments were performed in primary cultures of mouse hippocampal neurons. At a supratherapeutic concentration of 100 mu m, BRV was devoid of any direct effect on currents gated by -aminobutyric acidergic type A, glycine, kainate, N-methyl-D-aspartate, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid. Similarly to LEV, BRV reveals a potent ability to oppose the action of negative modulators on the inhibitory receptors. In conclusion, these results show that BRV contrasts with LEV by not displaying any direct action on inhibitory or excitatory postsynaptic ligand-gated receptors at therapeutic concentrations and thereby support BRV's role as a selective SV2A ligand. These findings add further evidence to the validity of SV2A as a relevant antiepileptic drug target and emphasize the potential for exploring further presynaptic mechanisms as a novel approach to antiepileptic drug discovery.
Notes: [Niespodziany, Isabelle; Matagne, Alain; Klitgaard, Henrik; Wolff, Christian] UCB Pharma, Braine Lalleud, Belgium. [Rigo, Jean-Michel] Hasselt Univ, Biomed Res Inst, Hasselt, Belgium. [Moonen, Gustave] Univ Liege, Sart Tilman Univ Hosp Ctr, Liege, Belgium.
URI: http://hdl.handle.net/1942/26290
DOI: 10.1111/epi.13890
ISI #: 000414363000002
ISSN: 0013-9580
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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