Brivaracetam: A rational drug discovery success story

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Abstract

Levetiracetam, the α-ethyl analogue of the nootropic piracetam, is a widely used antiepileptic drug (AED) that provides protection against partial seizures and is also effective in the treatment of primary generalized seizure syndromes including juvenile myoclonic epilepsy. Levetiracetam was discovered in 1992 through screening in audiogenic seizure susceptible mice and, 3 years later, was reported to exhibit saturable, stereospecific binding in brain to a ∼90 kDa protein, later identified as the ubiquitous synaptic vesicle glycoprotein SV2A. A large-scale screening effort to optimize binding affinity identified the 4-n-propyl analogue, brivaracetam, as having greater potency and a broadened spectrum of activity in animal seizure models. Recent phase II clinical trials demonstrating that brivaracetam is efficacious and well tolerated in the treatment of partial onset seizures have validated the strategy of the discovery programme. Brivaracetam is among the first clinically effective AEDs to be discovered by optimization of pharmacodynamic activity at a molecular target.

Original languageEnglish (US)
Pages (from-to)1555-1557
Number of pages3
JournalBritish Journal of Pharmacology
Volume154
Issue number8
DOIs
StatePublished - Aug 26 2008

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Keywords

  • λ-butyrolactam
  • Antiepileptic drug
  • Audiogenic seizures
  • Brivaracetam
  • Kindling
  • Levetiractam
  • Piracetam
  • Rational drug discovery
  • SV2A

ASJC Scopus subject areas

  • Pharmacology

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