BRIVARACETAM

Potency assay (off target): Brivaracetam was profiled at 10 μM (a concentration > 100 fold higher than its affinity for SV2A) against a panel of more than 55 targets comprising receptors, enzymes, ion channels and transporters. This panel included targets potentially involved in epilepsy such as GABAA (GABA and benzodiazepine binding sites), glycine, kainate, AMPA and NMDA receptors, L-type and N-type calcium channels, ATP and voltage dependent potassium channels, tetrodotoxin sensitive sodium channels, GABA transporter, glutamic acid decarboxylase (GAD) and the ryanodine receptor. Other targets screened were mostly G-protein coupled receptors (subtypes of adenosine, adrenergic, canabinoid, dopamine, histamine, opioid, muscarinic, neurokinine and serotonine receptors), transporters (adenosine, noradrenaline, dopamine and GABA) and enzymes (acetylcholinesterase, monoamine oxidase A and B). Brivaracetam did not bind, inhibit or activate any of the aforementioned targets. DOI: 10.1016/j.ejphar.2011.04.064

Potency assay, off target (cells): Results from SV2A−/− knock-out mice clearly show that up to concentrations of 600 nm, [3H]BRV specifically labels SV2A proteins: no binding could be observed in the brains of these knockout mice. Given the sensitivity of the binding assay, it is suggested that should BRV bind to other targets, it would probably occur in the high micromolar range at concentrations that are most likely not relevant to its overall mechanism of action. DOI:10.1111/epi.13340