Epileptiform seizures in domestic fowl. IX. Implications of the absence of anticonvulsant activity of ethosuximide in a pharmacological model of epilepsy.

Acute dose--response studies were conducted to determine if ethosuximide had anticonvulsant activity against seizures evoked by stroboscopic stimulation of epileptic fowl and to correlate the observed effects with the concentration of the drug in the plasma. Ethosuximide, in doses that produced mean plasma concentrations of 366 microgram/ml and signs of sedation, did not reduce seizure susceptibility. Twice daily administration of ethosuximide produced mean plasma concentrations of 430 microgram/ml after 36 h without affecting seizure susceptibility even in the presence of marked sedation. Previous studies have shown that epileptic fowl are sensitive to the anticonvulsant effects of phenobarbital, phenytoin, and primidone at plasma concentrations similar to those required in humans. Since ethosuximide has a high specificity against petit mal seizures in humans, the failure of ethosuximide to provide protection indicates that epileptic fowl represent a relatively specific pharmacological model for drugs effective against generalized tonic--clonic and focal cortical epilepsies in humans.