Open AccessBrivaracetam Differentially Affects Voltage‐Gated Sodium Currents Without Impairing Sustained Repetitive Firing in Neurons
Author(s) -
Niespodziany Isabelle,
André Véronique Marie,
Leclère Nathalie,
Ha Etienne,
Ghisdal Philippe,
Wolff Christian
Publication year - 2015
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12347
Subject(s) - sodium channel , chemistry , neuron , neuroscience , cortical neurons , pharmacology , epilepsy , biophysics , sodium , biology , organic chemistry
Summary Aims Brivaracetam ( BRV ) is an antiepileptic drug in Phase III clinical development. BRV binds to synaptic vesicle 2A ( SV 2A) protein and is also suggested to inhibit voltage‐gated sodium channels ( VGSC s). To evaluate whether the effect of BRV on VGSC s represents a relevant mechanism participating in its antiepileptic properties, we explored the pharmacology of BRV on VGSC s in different cell systems and tested its efficacy at reducing the sustained repetitive firing ( SRF ). Methods Brivaracetam investigations on the voltage‐gated sodium current ( I N a ) were performed in N1E‐155 neuroblastoma cells, cultured rat cortical neurons, and adult mouse CA 1 neurons. SRF was measured in cultured cortical neurons and in CA 1 neurons. All BRV (100–300 μM) experiments were performed in comparison with 100 μM carbamazepine ( CBZ ). Results Brivaracetam and CBZ reduced I N a in N1E‐115 cells (30% and 40%, respectively) and primary cortical neurons (21% and 47%, respectively) by modulating the fast‐inactivated state of VGSC s. BRV , in contrast to CBZ , did not affect I N a in CA 1 neurons and SRF in cortical and CA 1 neurons. CBZ consistently inhibited neuronal SRF by 75–93%. Conclusions The lack of effect of BRV on SRF in neurons suggests that the reported inhibition of BRV on VGSC currents does not contribute to its antiepileptic properties.