Brivaracetam inhibits spreading depression in rat neocortical slices in vitro

Epilepsy and migraine are episodic neurological disorders with marked co-morbidity, making migraine common among epileptic patients. Conversely, several antiepileptic drugs (AEDs) are used as migraine-preventive medication. Cortical spreading depression (CSD) represents a transient suppression of bioelectric activity and is considered a key event in migraine and stroke. This study assessed the novel AED candidate brivaracetam (BRV) vs. the chemically related AED levetiracetam in a rat neocortical slice model allowing consistent quantification of drug effects on CSD. CSD episodes were regularly elicited on slices upon delivery of calibrated KCl drops and were recorded via two micropipette electrodes. After control CSDs, the drug was added to the perfusion and five subsequent CSDs were elicited during drug perfusion. Effects were assessed via CSD amplitude (Ampl) and duration at half-amplitude (D(1/2)). BRV, 10 and 32 microM reduced the Ampl and transiently the D(1/2). Levetiracetam, 32 and 100 microM had no effect on either Ampl or D(1/2). The anti-CSD effect of BRV in this in vitro model might suggest a potential anti-migraine activity of this compound, which warrants further investigation.