A new antiepileptic drug
- 1Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK and National Hospital for Neurology and Neurosurgery London, UK, and the National Neuroscience Institute, Singapore
- 2Centre Neurologique William Lennox, Université Catholique de Louvain, Ottignies-Louvain La Neuve, Belgium
- Correspondence to: Professor S Shorvon, Institute of Neurology, University College London, Queen Square, London, WC1N 3BG, UK; s.shorvon{at}ion.ucl.ac.uk
- LEV, levetiracetam
- PTZ, pentylenetetrazol
- GABA, γ-aminobutyric acid
- GAD, glutamic acid decarboxylase
- SUDEP, sudden and unexplained death in epilepsy
Levetiracetam, a pyrrolidone recently licensed as an antiepileptic drug
Recently a new antiepileptic drug, levetiracetam (LEV), was approved for the add on treatment of partial epilepsy, both in the United States and in Europe. This is of potential importance, because this drug is from a class not previously used in epilepsy, although piracetam, a compound with a structure similar to that of levetiracetam, is useful in myoclonus. Both drugs are pyrrolidone derivatives, a class of drugs of interest for both psychotropic and nootropic applications and potentially as neuroprotectants. Levetiracetam (available under the registered trademark of UCB S.A., KeppraR) is the S-enantiomer of α-ethyl-2-oxo-1-pyrrolidine acetamide (fig 1). Homologues sharing the S configuration include a range of other compounds, some of which also have antiepileptic action.1 The range and extent of the compounds' activity in experimental models of epilepsy and other conditions varies considerably with minor changes to chemical structure, but the full extent of the range of properties of these drugs in humans has not been explored. This article reviews the experimental and clinical data relating to the antiepileptic action of levetiracetam.
Levetiracetam is a pyrrolidone derivative and is chemically designated (-)-(S)-α-ethyl-2-oxo-1-pyrrolidine acetamide. It has a molecular weight of 170.21 and molecular formula of C8H14N2O2.
EXPERIMENTAL STUDIES
Levetiracetam shows an unusual profile of antiepileptic activity in experimental animal models of partial and generalised epilepsy.2 Unlike other antiepileptic drugs, levetiracetam has no effect on tonic seizures induced by maximal electroshock or clonic seizures induced by pentylenetetrazol (PTZ) stimulation in the classic rodent models.2–4 It however has very marked protection against seizures in audiogenic mice, mice kindled with corneal electroshock or PTZ, and amygdaloid kindled rats. It protects against spontaneous spike and wave discharges in the GAERS model and in pilocarpine or …
