Network-specific mechanisms may explain the paradoxical effects of carbamazepine and phenytoin
Evan A Thomas, Steven Petrou
EPILEPSIA | WILEY | Published : 2013
PURPOSE: A common notion of the mechanism by which the antiepileptic drugs (AEDs) carbamazepine and phenytoin act is that they block sodium channels by binding preferentially to the inactivated state, thereby allowing normal neuronal firing while blocking ictal activity. However, these drugs have unpredictable efficacy and, in some cases, may exacerbate seizures. Previous studies have suggested that reducing sodium channel availability in the dentate gyrus (DG) paradoxically increases excitability. We used a biophysically detailed computer model of the DG to test the hypothesis that AEDs increase excitability by disproportionately reducing negative feedback mechanisms. METHODS: We built a Ma..View full abstract
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Awarded by National Health and Medical Research Council of Australia (NMHRC)
Awarded by NMHRC
This study is supported by National Health and Medical Research Council of Australia (NMHRC) program grant 400121 to S. P. S. P. acknowledges support from an NMHRC fellowship (1005050). The Florey Neuroscience Institutes are supported by Victorian State Government infrastructure funds. E. T. acknowledges the disappointing and consistent refusal of the NHMRC to fund mathematical modeling in neuroscience as a research activity for at least the last 15 years.