Antiepileptic Experimental Compound May Reduce Side Effects Associated with Conventional Treatments

Mar 31, 2016

Researchers at the University of Pittsburgh School of Medicine and Arts and Sciences say they have designed a more potent version of the FDA-approved epilepsy drug retigabine. A study published on March 22, 2016 in Molecular Pharmacology compares RL648_81 (RL-81), the experimental agent developed by Pitt researchers, with retigabine, and SF0034, a KCNQ2/3 activator being developed by SciFluor Life Sciences for suppressing neuronal hyperexcitability.

The researchers assert the new compound may not only be more potent than both SF0034 and retigabine, but it may also reduce the incidence of common side effects that are associated with antiepileptic drugs, including retinal abnormalities, skin discoloration, and urinary retention. According to the study, while there are more than 20 antiepileptic drugs available; 25–40% of those available are “refractory to the treatment” and are not without adverse side effects.

In comparison to other antiepileptic drugs, RL-81 is the “most potent KCNQ2/3-specific channel activator known to date,” according to researchers. The researchers add, “due to its higher, yet selective agonism on KNCQ2/3 channels, [RL-81] is expected to be more effective at a lower dose than retigabine and its analog, SF0034, in preventing seizures.” RL-81 does not activate the KCNQ4 or KCNQ5 channels, unlike retigabine, which adds to its specificity, and may mean it will have fewer side effects. The researchers note, RL-81 showed to be 15 times more potent than retigabine, and three times more potent than SF0034. The compound could also potentially be used to treat tinnitus, a disorder that causes ringing in the ears.

“At this point, the new compound is ready to be studied further in animal models of epilepsy and tinnitus and for other preclinical assessments,” said Peter Wipf, PhD, distinguished university professor of chemistry at Pitt. “RL-81 appears to have great potential for the treatment of these challenging neurological conditions.”

RL-81 is not the only drug being tested for its effectiveness at treating epilepsy. GW Pharmaceuticals, a London-base biopharmaceutical company recently released results from clinical trials with its drug Epidiolex (cannabidiol or CBD), an investigational drug meant to treat Dravet syndrome, a rare form of epilepsy. Phase III clinical trial results showed the drug achieved median reduction in monthly convulsive seizures of 39% over a 14-month treatment period.

In 2015, a report released by Pharmaceutical Manufacturers of America and the Epilepsy Foundation said the drug pipeline to treat neurological disorders included 420 medicines under review by FDA. The list includes drugs to treat epilepsy, in addition to Alzheimer’s disease, chronic pain, brain tumors, multiple sclerosis, Parkinson’s disease, migraine, spinal cord injury, neurological genetic disorders, and stroke.

Source: University of Pittsburgh School of Medicine

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