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This study investigated whether the mechanism of action of levetiracetam (LEV) is related to effects on neuronal voltage-gated Na+ or T-type Ca2+currents. Rat neocortical neurones in culture were subjected to the whole-cell mode of voltage clamping under experimental conditions designed to study voltage-gated Na+ current. Additionally, visually identified(More)
The effect of the new antiepileptic drug levetiracetam (LEV; KEPPRA) on the neuronal high-voltage-activated (HVA) Ca(2+) current was investigated on pyramidal neurones, visually identified in the CA1 area of rat hippocampal slices. Nystatin-perforated patch clamp recordings were made under experimental conditions designed to study HVA Ca(2+) currents. The(More)
Many antiepileptic drugs (AEDs) exert their therapeutic activity by modifying the inactivation properties of voltage-gated sodium (Na(v) ) channels. Lacosamide is unique among AEDs in that it selectively enhances the slow inactivation component. Although numerous studies have investigated the effects of AEDs on Na(v) channel inactivation, a direct(More)
The persistent Na+ current (INaP) has been proposed as the putative target of the anti-absence antiepileptic drugs. Accordingly, the effect of reference anti-absence drugs ethosuximide (ESM) and valproate (VPA), and of the new antiepileptic drug levetiracetam (LEV), on INaP have been tested in CA1 hippocampal neurons and compared to the classic(More)
AIMS 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(More)
The effect of levetiracetam on neuronal hypersynchrony and hyperexcitability was examined using simultaneous extra- and intracellular recordings in rat brain slices perfused with a high K+/low Ca2+ (HKLC) fluid. These findings were compared to results obtained with carbamazepine, valproate and clonazepam. The HKLC milieu induces in hippocampal CA3 area,(More)
Several antiepileptic drugs (AEDs) may induce memory deficits when tested in preclinical models at doses that exert significant protection against seizures. Brivaracetam (BRV) is a novel high-affinity SV2A ligand also displaying inhibitory activity at neuronal voltage-gated sodium channels. In the present study we have investigated the effects of BRV, at(More)
PURPOSE   In chronic epilepsy, a substantial proportion of up to 30% of patients remain refractory to antiepileptic drugs (AEDs). An understanding of the mechanisms of pharmacoresistance requires precise knowledge of how AEDs interact with their targets. Many commonly used AEDs act on the transient and/or the persistent components of the voltage-gated Na(+)(More)
OBJECTIVE Brivaracetam (BRV) decreases seizure activity in a number of epilepsy models and binds to the synaptic vesicle glycoprotein 2A (SV2A) with a higher affinity than the antiepileptic drug levetiracetam (LEV). Experiments were performed to determine if BRV acted similarly to LEV to induce or augment short-term depression (STD) under high-frequency(More)
The guinea-pig hypothalamic magnocellular dorsal nucleus (mdn) exclusively contains enkephalinergic neurones providing inputs to the septum. This nucleus is believed to play a role in hippocampo-septo-hypothalamic relationships. mdn neurones display prominent low-threshold Ca2+ spikes, which differ in their propensity to trigger either a burst of Na+ spikes(More)