Abstracts

RATIONALE: The anticonvulsant drug topiramate (TPM) has a broad spectrum of antiepileptic activity (3) and is clinically effective against simple or complex partial seizures and generalized tonic-clonic seizures in adults and children. The antiepileptic efficacy of TPM has been demonstrated in a variety of seizure models. Here, the antiepileptic effects of TPM were assessed in two models of genetically determined generalized epilepsy. The model of non-convulsive epilepsy used was a genetic model of absence seizures, the GAERS (Genetic Absence Epilepsy Rat from Strasbourg) and the model of convulsive seizures was a genetic audiogenic rat model, the Wistar AS.
METHODS: GAERS were equipped with four cortical electrodes over the fronto-parietal cortex and the duration of spike-and-wave discharges (SWDs) on the EEG was recorded for periods of 20 min up to 120 or 300 min after the injection of TPM. In Wistar AS, the occurrence of, latency to and duration of one or two wild running episodes and tonic seizures were recorded at 60 min after the injection of TPM.
RESULTS: In the 16 GAERS studied, TPM (10, 30 and 60 mg/kg) dose-dependently reduced the expression of SWDs that almost totally disappeared at the two highest doses between 40 and 120 min while 10 mg/kg TPM reduced the duration of SWDs by 42-72%. SWD duration returned to control levels by 180 and 280 min after the injection of 30 and 60 mg/kg TPM, respectively. In Wistar AS, 10 mg/kg TPM induced the occurrence of a second running episode not present in control rats, indicative of a decrease in sensitivity of the rats to the auditory stimulus and increased by 330% the latency to the tonic seizure that was still induced in the 8 rats studied. At 30 and 60 mg/kg TPM, the latency to wild running increased by 140%, the second running episode was suppressed in 6 and 7 rats, respectively while the tonic seizure occurred only in 1 of the 8 rats studied at these two doses.
CONCLUSIONS: The present results support the broad spectrum of antiepileptic activity of TPM confirming its efficacy in primary generalized seizures both of tonic/clonic nature and of the absence type.
[Supported by: a grant from Johnson and Johnson Pharmaceutical Research and Development, LLC.]; (Disclosure: Grant - Johnson and Johnson Pharmaceutical Research and Development, LLC)