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.
Stringer
J L
JL
Department of Pharmacology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. janets@bcm.tmc.edu
D000086:Acetazolamide / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D004353:Drug Evaluation, Preclinical; D005632:Fructose / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000188:drug therapy; D000077236:Topiramate
D000927:Anticonvulsants; D000077236:Topiramate; D005632:Fructose; D000086:Acetazolamide