By slightly modifying a drug currently used to treat epilepsy, researchers have come up with a new compound with the potential for superior efficacy in treating the disease, with fewer side effects. The bonus? The new compound may provide a way to prevent the development of tinnitus.
Explore this issue:August 2015
In a study published in the Journal of Neuroscience, investigators from the University of Pittsburgh and the University of Connecticut added a fluorine atom to retigabine (ezobagine in the U.S., recently approved by the Federal Drug Administration as an add-on to treat epilepsy) to produce the new compound (SF0034, SciFluor) that selectively affects potassium channels in the brain (2015;35:8829-8842). Pre-clinical data showed that, like retigabine, SF0034 helps to open the potassium channels (KCNQ) responsible for controlling neuronal excitability and acts as a brake to shut down the overly excited nerve signaling in brain disorders such as epilepsy and tinnitus.
The addition of the fluorine atom in SF0034 permits a greater selectivity by only opening two of the five potassium channels in the KCNQ family, whereas all five channels are opened when using retigabine. Due to the selectivity of SF0034, the compound was found to be less toxic and more potent in rodents and prevented the development of tinnitus in mice.
The need for a less toxic alternative to retigabine is highlighted by its associated toxicities, including dizziness, vertigo, tremor, confusion, urinary retention, vision changes, arrhythmia, psychiatric problems, and sleepiness, which have restricted its use. The investigators concluded that SF0034 provides not only a powerful tool for investigating ion channel properties, but, most importantly, it provides a clinical candidate for treating epilepsy and preventing tinnitus.
SciFluor now plans to start FDA trials with SF0034 to determine its safety and efficacy in humans.
Mary Beth Nierengarten is a freelance medical journalist based in Minnesota.