Abstracts

Rationale: Epilepsy and migraine being strongly associated co-morbid conditions, several antiepileptic drugs (AEDs) are used as migraine-preventive medication, as it is the tricyclic antidepressant amitriptyline. Cortical spreading depression (CSD), a transient suppression of bioelectric activity is a key event in migraine and stroke. Therefore, we assessed the candidate AED brivaracetam (BRV; ucb 34714) along with putative anti-migraine AEDs and amitriptyline in a rat neocortical slice model of CSD, recently described (Brain Res. Bull. 71, 23, 2006).Methods: CSD episodes were regularly elicited as DC transients (recorded via two micropipettes, spaced ~2.5 mm), upon delivery of calibrated ~nl drops of KCl, 3M on neocortical slices from ~6 weeks-old rats. After control CSDs, each drug was added to perfusion, at a concentration reportedly active on neurons, and five subsequent CSDs were elicited/attempted, under drug perfusion. Effects were assessed via CSD amplitude (Amp) and duration at half-amplitude (D_½).Results: BRV, 10 and 32 µM reduced the Amp and transiently the D_½, partly with concentration-dependence. Gabapentin, 100 µM only tended to lower Amp and D_½, after >1-h perfusion. Lamotrigine, 200 µM presented a modest similar tendency, noticeable but at the more distant recording point. Topiramate, 30 µM reduced the Amp of the early (<1-h in drug) CSDs, at the proximal recording point. Valproate, 2 mM presented non-significant tendencies to lower Amp and D_½, though it transiently increased D_½ at the proximal recording point. Amitriptyline, 30 µM reduced significantly D_½ at both recording points, while it enhanced Amp.Conclusions: BRV reduced CSD episodes, regularly elicited in vitro, with occasional concentration-dependence. Its anti-CSD effect in this slice model compares favorably with those of putative anti-migraine AEDs and amitriptyline. (Supported by UCB Pharma, Belgium)