Episode Details

In part one of this two-part series, Dr. Neishay Ayub discusses the history of a novel anti-epileptic drug, levetiracetam.

Show citations:

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Ulloa CM, Towfigh A, Safdieh J. Review of levetiracetam, with a focus on the extended release formulation, as adjuvant therapy in controlling partial-onset seizures. Neuropsychiatr Dis Treat. 2009;5:467-476. doi:10.2147/ndt.s4844

Wu PP, Cao BR, Tian FY, Gao ZB. Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil. Neurosci Bull. 2024;40(5):594-608. doi:10.1007/s12264-023-01138-2

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Show transcript:

Dr. Neishay Ayub:

Hello, my name is Neishay Ayub, and today we are discussing the history of a novel anti-epileptic drug, levetiracetam. It's a story of a scientific dead end, a radical new testing method, and a mystery that took years to unravel. To set the scene, let's go back to 1974. The pharmaceutical company, UCB Pharma, was working on compounds to boost cognitive function. They were looking for a successor to their drug piracetam. During this research, levetiracetam was first synthesized, but the compound didn't show any significant brain-boosting effects. With no discernible purpose, it was filed away and largely forgotten. For nearly two decades, this medicine sat on a shelf an anonymous entry in a long list of failed drug candidates. The story could have ended there, but in the early 1990s, researchers took a different approach to drug discovery. Researchers screened their entire library of forgotten compounds against audiogenic seizure-susceptible mice.

These are mice prone to seizures triggered by sound. Levetiracetam was incredibly ineffective in chronic epileptic mice. Interestingly, levetiracetam had previously failed traditional screening tests which was to prevent acute seizures in normal animals subjected to maximal electroshock or pentylenetetrazole. Levetiracetam was pushed forward to human clinical trials and was found to be efficacious in three placebo-co