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Drug prevents seizure progression in model of epilepsy
Date:5/4/2009

st seizure, BK channel function was markedly enhanced. As a result, the neurons became overly excitable and were firing with more speed, intensity and spontaneity, leading Barth to believe that the abnormal increased activity of the channels might play a role in causing subsequent seizures and the emergence of epilepsy.

In the current study, Barth tested this theory by blocking the ion channels using a BK-channel antagonist called paxilline. Using an experimental model for epilepsy, Barth asked whether paxilline could reduce or prevent experimentally induced seizures, as it could normalize aberrant brain activity induced by previous seizures. Remarkably, Barth and colleagues Jesse Sheehan and Brett Benedetti discovered that the compound was effective at completely blocking subsequent seizures.

"The drug is orally available, and works in the low nanomolar range," said Barth, noting that these characteristics, which mean the drug is effective in low concentrations and can be taken as a pill, make it an especially promising compound for treatment in epilepsy patients. While most anticonvulsants currently used to treat epilepsy work to directly inhibit the activity of neurotransmitters that causes seizures, few compounds interact with specific ion channels, especially potassium channels.

The researchers believe that targeting the BK channels and the abnormal brain activity that they induce might one day be used as a way to prevent the progression of seizure disorders over time, thus attacking the root cause of epilepsy.

According to Barth, the next steps will be to further investigate paxilline to see whether it is an effective anticonvulsant treatment for multiple types of seizures. The investigators continue to look at how BK channels are regulated by seizures to better understand the development of epilepsy.


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Contact: Jocelyn Duffy
jhduffy@andrew.cmu.edu
412-268-9982
Carnegie Mellon University
Source:Eurekalert

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