Stimulation-dependent effect of antiepileptic drugs in amygdala kindled rats on both seizure score and duration of afterdischarges.

The ED50 for abolition of generalized seizures and reduction of afterdischarges to 20% of the control duration was determined in kindled rats for phenobarbital, carbamazepine, phenytoin, valproic acid, clonazepam, and diazepam, both at a stimulation intensity of 200 microA and at 10 microA above the threshold for generalized seizures (threshold stimulation). Phenobarbital, carbamazepine, and valproic acid acted in a stimulus-dependent manner, i.e. the ED50 was higher at 200 microA than at threshold stimulation. Phenytoin had the same ED50 irrespective of the stimulus intensity. Generalized seizures and afterdischarges were suppressed by the same doses of the drugs mentioned. The benzodiazepines, clonazepam and diazepam, had a differential effect: they suppressed generalized seizures at low doses, whereas afterdischarges were only suppressed incompletely at relatively high doses. The ED50 of both benzodiazepines was independent of stimulus intensity. In order to avoid erroneous conclusions a standardization of kindling parameters, especially stimulation intensity, is proposed when drug effects are to be compared.