Development of SV2A Ligands for Epilepsy Treatment: A Review of Levetiracetam, Brivaracetam, and Padsevonil.

Epilepsy is a common neurological disorder that is primarily treated with antiseizure medications (ASMs). Although dozens of ASMs are available in the clinic, approximately 30% of epileptic patients have medically refractory seizures; other limitations in most traditional ASMs include poor tolerability and drug-drug interactions. Therefore, there is an urgent need to develop alternative ASMs.

Functional characterization and in vitro pharmacological rescue of KCNQ2 pore mutations associated with epileptic encephalopathy.

Mutations in the KCNQ2 gene encoding K7.2 subunit that mediates neuronal M-current cause a severe form of developmental and epileptic encephalopathy (DEE). Electrophysiological evaluation of KCNQ2 mutations has been proved clinically useful in improving outcome prediction and choosing rational anti-seizure medications (ASMs).

Discovery of HN37 as a Potent and Chemically Stable Antiepileptic Drug Candidate.

We previously reported that P-retigabine (P-RTG), a retigabine (RTG) analogue bearing a propargyl group at the nitrogen atom in the linker of RTG, displayed moderate anticonvulsant efficacy. Recently, our further efforts led to the discovery of (pynegabine), which demonstrated satisfactory chemical stability upon deleting the ortho liable -NH group and installing two adjacent methyl groups to the carbamate motif. exhibited enhanced activation potency toward neuronal Kv7 channels and high efficacy in a range of pre-clinical seizure models, including the maximal electroshock test and a 6 Hz model of pharmacoresistant limbic seizures.