当前位置： SCI文献检索 > EPILEPSIA期刊下所有文献 > Anticonvulsant efficacy of topiramate in phenytoin-resistant kindled rats.

Anticonvulsant efficacy of topiramate in phenytoin-resistant kindled rats.

Abstract：

PURPOSE:We evaluated the anticonvulsant efficacy of topiramate (TPM), a structurally novel antiepileptic drug (AED), in amygdala kindled rats that had been preselected with respect to their response to phenytoin (PHT). METHODS:Anticonvulsant response was tested by determining the afterdischarge threshold (ADT; i.e., a sensitive measure for drug effects on focal seizure activity). By repeated testing with the PHT prodrug fosphenytoin (FOS) three groups of kindled rats were separated: rats in which consistent anticonvulsant effects were obtained (PHT responders), rats that showed no anticonvulsant response (PHT nonresponders), and rats with variable responses (variable PHT responders). The latter, largest group was used to evaluate at which doses and pretreatment times TPM exerted significant anticonvulsant effects on ADT. For this purpose, TPM was tested at four doses (20, 40, 80, 160 mg/kg i.p.) and two pretreatment times (1 and 4 h). The most effective treatment protocol was then used for TPM testing in PHT responders and nonresponders. RESULTS:TPM proved to be an effective AED in the kindling model. At 40 mg/kg, significant ADT increases were obtained after both 1 and 4 h after administration. In addition to the effect on focal seizure threshold, seizure severity and duration recorded at ADT were decreased by TPM, indicating that this drug acts on both seizure threshold and seizure spread. In PHT nonresponders, TPM significantly increased ADT, which is in line with its proven efficacy in patients with refractory partial epilepsy in whom phenytoin has failed. However, TPM was more efficacious in increasing ADT in PHT responders than in nonresponders, substantiating that the difference between these groups of kindled rats extends to other AEDs. Repeated testing of kindled rats with TPM indicated that, similar to PHT, there are individual kindled rats without anticonvulsant response to TPM (i.e., TPM nonresponders). CONCLUSIONS:The data of this study substantiate that PHT nonresponders are a unique model for the search of new AEDs with improved efficacy in refractory partial epilepsy.

journal_name

Epilepsia

journal_title

Epilepsia

authors

Reissmüller E,Ebert U,Löscher W

doi

10.1111/j.1528-1157.2000.tb00176.x

subject

Has Abstract

pub_date

2000-04-01 00:00:00

pages

372-9

issue

eissn

0013-9580

issn

1528-1167

journal_volume

pub_type

杂志文章

在线工具

Anticonvulsant efficacy of topiramate in phenytoin-resistant kindled rats.