Effect of stimulus intensity on the profile of anticonvulsant activity of phenytoin, ethosuximide and valproate.

The relative ability of phenytoin, ethosuximide and valproate to prevent minimal (clonic) threshold, maximal (tonic extension of the hindlimbs) threshold and supramaximal (tonic extension of the hindlimbs) seizures elicited by electrical and chemical (Metrazol, bicuculline, and picrotoxin) stimulation was determined. Ethosuximide and valproate were effective against minimal (clonic) threshold seizures, whereas phenytoin was ineffective and even activated them. All three anticonvulsants were effective against maximal (tonic extension of the hindlimbs) threshold seizures. Phenytoin and valproate, but not ethosuximide, were effective against supramaximal (tonic extension of the hindlimbs) seizures. The results suggest that the specificity of experimental models of epilepsy used in the evaluation of potential antiepileptic drugs is primarily due to the intensity rather than the nature of the stimulus used or the kind of seizure component evoked. Models based only on maximal (tonic extension of the hindlimbs) threshold seizures may identify anticonvulsant activity, but do not differentiate between substances that prevent seizure spread and those that increase seizure threshold.