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New Pharmacological Insights into The Epilepsy Drug Retigabine

by Dr. Trupti Shirole on February 19, 2016 at 8:45 AM
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 New Pharmacological Insights into The Epilepsy Drug Retigabine

Epilepsy is a family of encephalopathies characterized by abnormal synchronous and rhythmic neuronal activity in the brain that results in seizures. It is one of the most common disorders of the brain and has been diagnosed in 5.1 million people in the United States, revealed the Centers for Disease Control and Prevention.

Retigabine is a known pharmacological treatment for epilepsy. A study published in the The Journal of General Physiology has revealed new insights into Retigabine.

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The heteromeric neuronal KV7.2/KV7.3 channel is the assembly of KV7 subunits most commonly found in the central nervous system. Mutations that detrimentally affect the function of neuronal KV7 channels cause hyperexcitability syndromes such as benign familial neonatal seizures, early onset epileptic encephalopathy, and peripheral nerve hyperexcitability. Pharmacotherapeutic approaches using drugs such as Retigabine have therefore been implemented to boost the activity of KV7 channels.

However, detailed understanding of the molecular basis for the role of neuronal KV7 channels in hyperexcitability syndromes has been lacking.
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In their study using Xenopus laevis oocytes, Aaron Corbin-Leftwich, an undergraduate student at Virginia Commonwealth University, School of Medicine in Richmond, VA, under Carlos A. Villalba-Galea, assistant professor in the Department of Physiology and Biophysics, and colleagues found that Retigabine reduces excitability by enhancing the resting potential open state stability of KV7.2/KV7.3 channels. The stabilization of the channels that are already opened at neuronal resting potential levels is the clinically relevant effect of the anticonvulsant.

The authors noted, "Retigabine binds to KV7 proteins, causing them to stay open for longer. This allows for a larger flow of potassium ions that are leaving the neuron. This increases the magnitude of the stimulation required to excite neurons, decreasing the chance of spontaneous activity, and reducing unwanted electrical signals."

These findings may help in further refinement of the available pharmacotherapy for KV7-related encephalopathies, as well as for the design of new ones.

Source: Eurekalert
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