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 of BRV on VGSCs in different cell syst...

Antiepileptic drugs (AEDs) vary in their efficacy against generalized tonic-clonic, myoclonic, and absence seizures, suggesting different mechanisms of action. Phenytoin (PHT), carbamazepine (CBZ), and valproate (VPA) reduced the ability of mouse central neurons to sustain high-frequency repetitive firing of action potentials (SRF) at therapeutic free serum concentrations. Phenobarbital (PB) an...

In deeply anesthetized mammals, as typified by the adult cat, there is limited evidence that the firing-rate response of spinal motor neurons to sustained stimulation usually features a progressive reduction in firing rate, termed late adaptation, that begins 1 2 s after the onset of sustained stimulation. The fullest description of late adaptation has been provided by Kernell & Monster (1982a,...

The effect of cycle length on atrial vulnerability was studied in 14 patients manifesting reproducible repetitive atrial firing during atrial extra-stimulus (A2) testing. Repetitive atrial firing was defined as the occurrence of two or more premature atrial responses with return cycle (A2-A3) of 250 msec or less and subsequent mean cycle length of 300 msec or less, following A2. The zone of rep...

The SNS SRF system is operated with a pulsed beam. For the SRF system to track the repetitive reference trajectory, a feedback and a feedforward controllers has been proposed. The feedback controller is to guarantee the closed loop system stability and the feedforward controller is to improve the tracking performance for the repetitive reference trajectory and to suppress the repetitive disturb...

We compared membrane and synaptic properties of neurons in the three major subdivisions of inferior colliculus (IC), central nucleus (ICc, N=18), external cortex (ICx, N=38), and dorsal cortex (ICd, N=31) of slices from rat IC, using intracellular neuronal recording. Three types of responses occurred in each IC subdivision in response to depolarizing currents: on-type (N=20), rapidly-adapting (...

The operation of neuronal networks depends on the firing patterns of the network's neurons. When sustained current is injected, some neurons in the central nervous system fire a single action potential and others fire repetitively. For example, in Xenopus laevis tadpoles, primary-sensory Rohon-Beard (RB) neurons fired a single action potential in response to 300-ms rheobase current injections, ...

Established antiepileptic drugs (AEDs) decrease membrane excitability by interacting with neurotransmitter receptors or ion channels. AEDs developed before 1980 appear to act on sodium channels, gamma-aminobutyric acid type A (GABAA) receptors, or calcium channels. Benzodiazepines and barbiturates enhance GABAA receptor-mediated inhibition. Phenytoin (PHT), carbamazepine (CBZ), and possibly val...