The exact mechanism of action of ethosuximide is not entirely understood. Ethosuximide inhibits NADPH-linked aldehyde reductase necessary for the formation of gamma-hydroxybutyrate, which has been associated with the induction of absence seizures. Ethosuximide also appears to inhibit the sodium-potassium ATPase system. Ethosuximide can decrease the burst firing of thalamocortical neurons. This action may explain the anti-absence activity of the drug.

Ethosuximide also has been shown to decrease non-inactivating Na currents in thalamocortical neurons, as well as blocking Ca dependent K channels.

It does not appear to alter brain GABA concentrations.

Reviewed February 2004 by Barry Gidal, PharmD, epilepsy.com Editorial Board.