Epilepsy Drug "Quiets" Nerve Cells

A drug commonly used to prevent seizures in patients with epilepsy apparently works by binding to a part of nerve cells called dendrites and making that portion less excitable, said Baylor College of Medicine researchers in a report in the July issue of the journal Nature Neuroscience.

"This is the first demonstration of a drug in the central nervous system targeting this specific part of a neuron (nerve cell)," said Daniel Johnston, Ph.D., professor of neuroscience at Baylor. "This is a very novel mechanism. This drug is very effective in treating epilepsy and in other disorders such as bipolar disease and pain."

Johnston said the mechanism discovered in his lab could be used by drug companies hoping to find more effective ways to treat these problems.

Dendrites are branched structures arising from the nerve cell that gather incoming electrical information from other nerve cells. The drug, called lamotrigine, acts on a newly discovered type of ion channel that clusters in dendrites. By affecting only the dendrites, the drug isolates the nerve cell from the excitatory influences of surrounding cells, making it less likely to excite other nerve cells in turn.

When it binds to the channel, lamotrigine opens it. The reaction is similar to that seen when someone puts a hole in a water hose, said Johnston. Just as the water pressure from the hose drops because water is also coming out of the new hole, electrical current in the dendrites is shunted out through this channel, reducing the neuron’s ability to fire electrical impulses.

"Epilepsy is a disease of too much excitability," said Johnston. "This drugs make the nerve cells less excitable by opening up these channels." His group has yet to determine why it has an effect on psychiatric problems such as bipolar disorder or on pain.

This study was partially funded by the Hankamer Foundation and the National Institutes of Health. Other researchers include: Nicholas P. Poolos, Ph.D., formerly of Baylor and now at the University of Washington in Seattle and, Michele Migliore, Ph.D., National Research Council, Institute of Advanced Diagnostic Methodologies in Palermo, Italy.

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©2006 Texas Medical Center

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