Anti-seizure drugs are the most commonly employed treatment option for
epilepsy and these generally provide effective management of
seizures. However, 30% of patients with
epilepsy are not adequately treated with anti-seizure medications and are considered intractable. Recently we reported that
isovaline, a unique
amino acid, could attenuate seizure like events (SLEs) in two in vitro hippocampal seizure models by selectively increasing the activity of interneurons, but not pyramidal neurons.
Isovaline also attenuated hippocampal epileptiform activity and behavioral
seizures in vivo in rats administered
4 aminopyridine (4AP). Here, we investigate whether
isovaline is efficacious in attenuating secondarily generalized epileptiform activity and behavioral
seizures in rats administered
pilocarpine. We found that 150 mg/kg
isovaline administered intravenously abolished
pilocarpine-induced epileptiform activity in the primary sensory cortex and hippocampus and attenuated generalized forebrain behavioral
seizures. We are the first to demonstrate that
isovaline may be a plausible anti-seizure
drug for secondarily
generalized seizures and this could potentially lead to the development of a novel class of anti-seizure drugs focused around the unique mechanism(s) of
isovaline.