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Pfizer Inc.

Drug Names(s): Ethosuximide

Description: Zarontin (ethosuximide) is a succinimide anticonvulsant. Zarontin suppresses the paroxysmal three cycle per second spike and wave activity associated withlapses of consciousness which is common in absence (petit mal) seizures. The frequency of epileptiformattacks is reduced, apparently by depression of the motor cortex and elevation of the threshold of thecentral nervous system to convulsive stimuli.

The exact mechanism of action of Ethosuximide is not entirely understood. Ethosuximideselectively blocks transient (“T-type”) calcium currents in thalamic neurons, which inhibits the thalamocorticalcircuits responsible for generating the EEG spike-wave complex underlying absence seizures.Ethosuximide also 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 sodium currents in thalamocortical neurons, as well as blocking Ca++ dependent potassium channels.

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