Abstract
Antiepileptic drugs act on voltage gated sodium channels in many different ways: rufinamide is thought to influence the fast inactivation, so its anticonvulsant action could be similar to carbamazepine, whereas lacosamide enhances the slow inactivation; however some antidepressants were also described to act in the same way. Rufinamide, lacosamide, carbamazepine, fluoxetine and imipramine were tested using in vitro models of epileptiform activities. Extracellular local field potentials were recorded using hippocampal slices from immature rats and the pattern of epileptiform activities was analyzed. Seizure-like events (SLE), but not interictal bursts were sensitive to AEDs’ action. Rufinamide increased interictal periods by prolonging preictal phase and reducing SLE duration, and was the only tested AED which reduced SLE frequency. Lacosamide’s effect resembled that of fluoxetine in the low-Mg2+ model: both drugs reduced markedly the SLE duration, but increased their frequency. Imipramine and fluoxetine irreversibly suppressed SLE in all slices. Some proconvulsive type of action on SLEs such as increasing preictal neuronal activity by rufinamide and increasing SLE frequency by lacosamide, fluoxetine and carbamazepine, were also observed. Newer drugs were more efficient than carbamazepine, and the anticonvulsant action of antidepressants on in vitro epileptiform activities may seem somewhat surprising.
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Acknowledgments
This paper was published under the frame of European Social Found, Human Resources Development Operational Programme 2007–2013, Project No. POSDRU/159/1.5/S/136893. The authors thank MSN Laboratories Limited. (India) and Hetero Drugs Limited (India) for kindly supplying the drugs used in this study—rufinamide and lacosamide, respectively.
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Gáll, Z., Orbán-Kis, K. & Szilágyi, T. Differential effects of sodium channel blockers on in vitro induced epileptiform activities. Arch. Pharm. Res. 40, 112–121 (2017). https://doi.org/10.1007/s12272-015-0676-6
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DOI: https://doi.org/10.1007/s12272-015-0676-6