Chapter 3 - Mechanisms of Action of Levetiracetam and Newer SV2A Ligands

Abstract

This chapter describes the epilepsy pharmacology and reviews the mechanisms of action of levetiracetam (LEV), brivaracetam (BRV), and seletracetam (SEL). LEV is the (S)-enantiomer of the ethyl analog of the nootropic drug piracetam. BRV differs from both LEV and SEL by inducing seizure protection, albeit at relatively high doses, against maximal electroshock and pentylenetetrazol seizures in mice. SEL resembles LEV, but differs from BRV, by its absence of activity against maximal electroshock and pentylenetetrazol seizures in mice. BRV and SEL represent the first successful outcome of efforts focused on generating optimized, high-affinity SV2A ligands. They are both superior to LEV with respect to their affinity for SV2A and their ability to provide seizure protection in vivo. But they differ significantly, in particular by their effect on other relevant antiepileptic mechanisms, a finding further supported by their distinct profile in in vitro and in vivo models of epilepsy. Taken together, this highlights the promise that both may represent an important addition to the existing armamentarium of AEDs available for the treatment of epilepsy.