Journal article

Network-specific mechanisms may explain the paradoxical effects of carbamazepine and phenytoin

Evan A Thomas, Steven Petrou

EPILEPSIA | WILEY | Published : 2013

Abstract

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..

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Grants

Awarded by National Health and Medical Research Council of Australia (NMHRC)


Awarded by NMHRC


Funding Acknowledgements

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.