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. 2007 Jun 9;13(2):224–239. doi: 10.1111/j.1527-3458.2007.00009.x

Ethosuximide: From Bench to Bedside

M Zafer Gören 1, Filiz Onat 1
PMCID: PMC6528725  PMID: 17627674

ABSTRACT

Ethosuximide, 2‐ethyl‐2‐methylsuccinimide, has been used extensively for “petit mal” seizures and it is a valuable agent in studies of absence epilepsy. In the treatment of epilepsy, ethosuximide has a narrow therapeutic profile. It is the drug of choice in the monotherapy or combination therapy of children with generalized absence (petit mal) epilepsy. Commonly observed side effects of ethosuximide are dose dependent and involve the gastrointestinal tract and central nervous system. Ethosuximide has been associated with a wide variety of idiosyncratic reactions and with hematopoietic adverse effects. Typical absence seizures are generated as a result of complex interactions between the thalamus and the cerebral cortex. This thalamocortical circuitry is under the control of several specific inhibitory and excitatory systems arising from the forebrain and brainstem. Corticothalamic rhythms are believed to be involved in the generation of spike‐and‐wave discharges that are the characteristic electroencephalographic signs of absence seizures. The spontaneous pacemaker oscillatory activity of thalamocortical circuitry involves low threshold T‐type Ca2+ currents in the thalamus, and ethosuximide is presumed to reduce these low threshold T‐type Ca2+ currents in thalamic neurons. Ethosuximide also decreases the persistent Na+ and Ca2+‐activated K+ currents in thalamic and layer V cortical pyramidal neurons. In addition, there is evidence that in a genetic absence epilepsy rat model ethosuximide reduces cortical γ‐aminobutyric acid (GABA) levels. Also, elevated glutamate levels in the primary motor cortex of rats with absence epilepsy (but not in normal animals) are reduced by ethosuximide.

Keywords: Anticonvulsants, Ca2+ currents, Epilepsy, Epileptic rats (GAERS), Ethosuximide, γ‐aminobutyric acid (GABA), Glutamate, K+currents, Myoclonic seizures, Na+currents, Nitric oxide (NO), Pain, Thalamus

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Acknowledgments

Acknowledgments We thank Professor Emeritus Ray Guillery from the University of Wisconsin Medical School, Department of Anatomy for editing English in the manuscript.

Conflict of Interest: The authors have no conflicts of interest.

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