Detailed Instructions: Given a passage with a context and an answer, construct a question on the basis of the information present in the passage. Construct the question in such a way that (i) it is unambiguous, (ii) it is answerable from the passage, (iii) its answer is unique (iv) it answer uses text phrases from the passage. Avoid creating questions that (i) can't be answered correctly without actually understanding the passage and (ii) uses the same words or phrases given in the passage.
Problem:Context: Brivaracetam (BRV) is an antiepileptic drug in Phase III clinical development. BRV binds to synaptic vesicle 2A (SV2A) protein and is also suggested to inhibit voltage-gated sodium channels (VGSCs). To evaluate whether the effect of BRV on VGSCs represents a relevant mechanism participating in its antiepileptic properties, we explored the pharmacology of BRV on VGSCs in different cell systems and tested its efficacy at reducing the sustained repetitive firing (SRF).', 'Brivaracetam investigations on the voltage-gated sodium current (I(Na)) were performed in N1E-155 neuroblastoma cells, cultured rat cortical neurons, and adult mouse CA1 neurons. SRF was measured in cultured cortical neurons and in CA1 neurons. All BRV (100-300 M) experiments were performed in comparison with 100 M carbamazepine (CBZ).', 'Brivaracetam and CBZ reduced IN a in N1E-115 cells (30% and 40%, respectively) and primary cortical neurons (21% and 47%, respectively) by modulating the fast-inactivated state of VGSCs. BRV, in contrast to CBZ, did not affect I(Na) in CA1 neurons and SRF in cortical and CA1 neurons. CBZ consistently inhibited neuronal SRF by 75-93%.
Answer: 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.
Solution:
Does brivaracetam differentially affect voltage-gated sodium currents without impairing sustained repetitive firing in neurons?