Anti-convulsive and anti-epileptic properties of brivaracetam (ucb 34714), a high-affinity ligand for the synaptic vesicle protein, SV2A
Version of Record online: 29 JAN 2009
2008 British Pharmacological Society
British Journal of Pharmacology
Volume 154, Issue 8, pages 1662–1671, August 2008
How to Cite
Matagne, A., Margineanu, D.-G., Kenda, B., Michel, P. and Klitgaard, H. (2008), Anti-convulsive and anti-epileptic properties of brivaracetam (ucb 34714), a high-affinity ligand for the synaptic vesicle protein, SV2A. British Journal of Pharmacology, 154: 1662–1671. doi: 10.1038/bjp.2008.198
- Issue online: 29 JAN 2009
- Version of Record online: 29 JAN 2009
- (Received December 7, 2007, Revised February 26, 2008, Accepted April 14, 2008)
- antiepileptic effect;
- anticonvulsive effect;
- safety profile;
- synaptic vesicle protein;
Background and purpose:
Screening of 12 000 compounds for binding affinity to the synaptic vesicle protein 2A (SV2A), identified a high-affinity pyrrolidone derivative, brivaracetam (ucb 34714). This study examined its pharmacological profile in various in vitro and in vivo models of seizures and epilepsy, to evaluate its potential as a new antiepileptic drug.
The effects of brivaracetam and levetiracetam on epileptiform activity and seizure expression were examined in rat hippocampal slices, corneally kindled mice, audiogenic seizure–susceptible mice, maximal electroshock and pentylenetetrazol seizures in mice, hippocampal-kindled rats, amygdala-kindled rats and genetic absence epilepsy rats.
Brivaracetam and levetiracetam reduced epileptiform responses in rat hippocampal slices, brivaracetam being most potent. Brivaracetam also differed from levetiracetam by its ability to protect against seizures in normal mice induced by a maximal electroshock or maximal dose of pentylenetetrazol. In corneally kindled mice and hippocampal-kindled rats, brivaracetam induced potent protection against secondarily generalized motor seizures and showed anti-kindling properties superior to levetiracetam. In amygdala-kindled rats, brivaracetam induced a significant suppression in motor-seizure severity and, contrary to levetiracetam, reduced the after-discharge at a higher dose. Audiogenic seizure–susceptible mice were protected more potently against the expression of clonic convulsions by brivaracetam than by levetiracetam. Brivaracetam induced a more complete suppression of spontaneous spike-and-wave discharges in genetic absence epilepsy rats than levetiracetam.
Conclusions and implications:
Brivaracetam has higher potency and efficacy than levetiracetam as an anti-seizure and anti-epileptogenic agent in various experimental models of epilepsy, and a wide therapeutic index.
British Journal of Pharmacology (2008) 154, 1662–1671; doi:fn1; published online 26 May 2008