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• W3140776622 endingPage "369" @default.
• W3140776622 startingPage "369" @default.
• W3140776622 abstract "Brivaracetam (BRV) is recognized as a novel third-generation antiepileptic drug approved for the treatment of epilepsy. Emerging evidence has demonstrated that it has potentially better efficacy and tolerability than its analog, Levetiracetam (LEV). This, however, cannot be explained by their common synaptic vesicle-binding mechanism. Whether BRV can affect different ionic currents and concert these effects to alter neuronal excitability remains unclear. With the aid of patch clamp technology, we found that BRV concentration dependently inhibited the depolarization-induced M-type K+ current (IK(M)), decreased the delayed-rectifier K+ current (IK(DR)), and decreased the hyperpolarization-activated cation current in GH3 neurons. However, it had a concentration-dependent inhibition on voltage-gated Na+ current (INa). Under an inside-out patch configuration, a bath application of BRV increased the open probability of large-conductance Ca2+-activated K+ channels. Furthermore, in mHippoE-14 hippocampal neurons, the whole-cell INa was effectively depressed by BRV. In simulated modeling of hippocampal neurons, BRV was observed to reduce the firing of the action potentials (APs) concurrently with decreases in the AP amplitude. In animal models, BRV ameliorated acute seizures in both OD-1 and lithium-pilocarpine epilepsy models. However, LEV had effects in the latter only. Collectively, our study demonstrated BRV’s multiple ionic mechanism in electrically excitable cells and a potential concerted effect on neuronal excitability and hyperexcitability disorders." @default.
• W3140776622 created "2021-04-13" @default.
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• W3140776622 date "2021-04-01" @default.
• W3140776622 modified "2023-10-03" @default.
• W3140776622 title "The Integrated Effects of Brivaracetam, a Selective Analog of Levetiracetam, on Ionic Currents and Neuronal Excitability" @default.
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• W3140776622 doi "https://doi.org/10.3390/biomedicines9040369" @default.
• W3140776622 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8067033" @default.
• W3140776622 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33916190" @default.
• W3140776622 hasPublicationYear "2021" @default.
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