Ethosuximide is a succinimideanticonvulsant, used mainly in absence seizures. It is sold by Pfizer under the name Zarontin® and was once also sold under the name Emeside®, both of which were discontinued from the United Kingdom market in capsule form in November of 2005.
Uses
Approved
It is approved for absence seizures.
Unapproved
It was reported to have been used for intermittent explosive disorder in 1980 by Drs Andrulonis, Donnelly, Glueck, Stroebel, and Szabek.
Mechanism of Action
There is some controversy over the exact mechanism by which ethosuximide prevents absence seizures. While the "ethosuximide is a T-type calcium channel blocker" gained widespread support following its proposal, attempts to replicate the initial finding were inconsistent.
In March of 1989, Coulter, Huguenard and Prince showed that ethosuximide and dimethadione, both effective anti-absence agents, reduced low-threshold Ca2+currents in T-type Ca2+ channels in freshly removed thalamicneurons. In June of that same year, they also found the mechanism of this reduction to be voltage-dependent, using acutely neurons of rats and guinea pigs; it was also noted that valproic acid, which is also used in absence seizures, did not do that. The next year, they showed that anticonvulsant succinimides did this and that the proconvulsant ones did not. The first part was supported by Kostyuk et al in 1992, who reported a substantial reduction in current in dorsal rootganglia at concentrations ranging from 7 μM to 1 mM.
That same year, however, Herrington and Lingle found no such effect at concentrations of up to 2.5 mM. The year after, a study conducted on human neocortical cells removed during surgery for intractable epilepsy, the first to use human tissue, found that ethosuximide had no effect on Ca2+ currents at the concentrations typically needed for a therapeutic effect.
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