title: Isovaline attenuates generalized epileptiform activity in hippocampal and primary sensory cortices and seizure behavior in pilocarpine treated rats.
abstract: 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.
authors.affiliation: Center for Neuropharmacology & Neuroscience, Albany Medical College, 47 New Scotland Ave Albany, NY, USA.
authors.forename: Wilson
authors.initials: W
authors.lastname: Yu
authors.affiliation: Center for Neuropharmacology & Neuroscience, Albany Medical College, 47 New Scotland Ave Albany, NY, USA.
authors.forename: Autumn B
authors.initials: AB
authors.lastname: Smith
authors.affiliation: Center for Neuropharmacology & Neuroscience, Albany Medical College, 47 New Scotland Ave Albany, NY, USA; Division of Neurosurgery, Albany Medical Center, 47 New Scotland Ave Albany, NY, USA.
authors.forename: Julie G
authors.initials: JG
authors.lastname: Pilitsis
authors.affiliation: Center for Neuropharmacology & Neuroscience, Albany Medical College, 47 New Scotland Ave Albany, NY, USA. Electronic address: shind@mail.amc.edu.
authors.forename: Damian S
authors.initials: DS
authors.lastname: Shin
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology* / Q000627:therapeutic use; D004829:Epilepsy, Generalized / Q000139:chemically induced / Q000503:physiopathology*; D006624:Hippocampus / Q000187:drug effects* / Q000503:physiopathology; D008297:Male; D010862:Pilocarpine; D017207:Rats, Sprague-Dawley; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013003:Somatosensory Cortex / Q000187:drug effects* / Q000503:physiopathology; D014633:Valine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D010862:Pilocarpine; C032737:isovaline; D014633:Valine
keywords: Anticonvulsant; Antiepileptic drug; Epilepsy; Hippocampus; Seizure; Temporal lobe epilepsy