Abstract

The effects of three new antiepileptic drugs (felbamate, lamotrigine and gabapentin) on the parameters of seizure initiation and termination in one model of reverberatory seizures in the hippocampal-parahippocampal loop in urethane-anesthetized rats were determined. All three of the drugs caused a dose-dependent decrease in the duration of the seizure discharge. Only very high doses of felbamate had a significant effect on seizure initiation. In addition to the seizure model, we tested the three new anti-epileptic drugs for an effect on excitability, on paired-pulse inhibition and on long-term potentiation (LTP) in the dentate gyrus of the urethane-anesthetized rat. None of the drugs altered LTP or excitability. However, gabapentin altered paired-pulse inhibition, causing a loss of inhibition. For felbamate and lamotrigine, the effects of seizure duration are consistent with their clinical effects as antiepileptic drugs. However, the effect of gabapentin on paired-pulse inhibition suggests a proconvulsant effect and the effect on seizure duration suggests an antiepileptic effect.

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