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Differential effects of sodium channel blockers on in vitro induced epileptiform activities
Zsolt Ga´ ll,Ka´roly Orba´n-Kis,Tibor Szila´gyi 대한약학회 2017 Archives of Pharmacal Research Vol.40 No.1
Antiepileptic drugs act on voltage gated sodiumchannels in many different ways: rufinamide is thought toinfluence the fast inactivation, so its anticonvulsant actioncould be similar to carbamazepine, whereas lacosamideenhances the slow inactivation; however some antidepressantswere also described to act in the same way. Rufinamide,lacosamide, carbamazepine, fluoxetine andimipramine were tested using in vitro models of epileptiformactivities. Extracellular local field potentials were recordedusing hippocampal slices from immature rats and the patternof epileptiform activities was analyzed. Seizure-like events(SLE), but not interictal bursts were sensitive to AEDs’action. Rufinamide increased interictal periods by prolongingpreictal phase and reducing SLE duration, and was theonly tested AED which reduced SLE frequency. Lacosamide’seffect resembled that of fluoxetine in the low-Mg2?model: both drugs reduced markedly the SLE duration, butincreased their frequency. Imipramine and fluoxetine irreversiblysuppressed SLE in all slices. Some proconvulsivetype of action on SLEs such as increasing preictal neuronalactivity by rufinamide and increasing SLE frequency bylacosamide, fluoxetine and carbamazepine, were alsoobserved. Newer drugs were more efficient than carbamazepine,and the anticonvulsant action of antidepressantson in vitro epileptiform activities may seem somewhatsurprising.
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