A comparison of topiramate and acetazolamide on seizure duration and paired-pulse inhibition in the dentate gyrus of the rat

Topiramate is a relatively new antiepileptic drug with several putative anticonvulsant mechanisms. Among them is the ability to inhibit carbonic anhydrase, a property in common with the anticonvulsant acetazolamide. This study examined the effects of topiramate and acetazolamide on the duration of epileptiform activity and on paired-pulse inhibition in the dentate gyrus in urethane anesthetized adult Sprague–Dawley rats. Neither topiramate nor acetazolamide altered excitability in the dentate gyrus, as measured with input–output curves or induction of long-term potentiation. Topiramate increased paired-pulse inhibition, whereas acetazolamide had no effect. Both drugs dose-dependently blocked the lengthening of the duration of epileptiform activity compared to vehicle controls. These results indicate that topiramate has an anticonvulsant-related effect (increase in paired-pulse inhibition), which may contribute to its antiepileptic effect, that is not dependent on its ability to inhibit carbonic anhydrase.