Isovaline attenuates epileptiform activity and seizure behavior in 4-aminopyridine treated rats

Epilepsy is the most common neurological disorder in the world and although there are various treatment options available, 30% of patients remain intractable. Current antiepileptic drugs (AEDs) provide efficacy primarily by decreasing excitation or increasing inhibition in the seizing brain. Isovaline, a unique amino acid, was shown to attenuate seizure-like events (SLEs) in two in vitro hippocampal seizure models by selectively increasing the activity of interneurons, but not pyramidal neurons. Here, we demonstrate that 4-aminopyridine (4-AP) induced hippocampal epileptiform activity in vivo and seizing behavior, which were attenuated with intravenous (IV) isovaline treatment. We are the first to demonstrate that isovaline has potential as an AED and a conceptual framework for managing epilepsy could revolve around its novel mechanism of action.