The aim of this study was to investigate the potential effect of lacosamide (LCM) on migraine pathophysiology using an in vivo model of cortical spreading depolarization (CSD).

Although new drugs have emerged in the migraine field in recent years, there remains an unmet need for novel therapeutics. Drug repositioning of existing agents may represent a viable option. Antiseizure medications are frequently used for migraine prevention; however, the efficacy of LCM, a sodium channel blocker, in preventing migraine attacks remains unclear. CSD is characterized by a slowly propagating wave of neuronal and glial depolarization across the cerebral cortex and is considered a key mechanism underlying migraine aura. Animal models of CSD are widely used to evaluate the pharmacological effects of possible migraine therapies.

We evaluated the effects of a single dose of LCM (40 mg/kg) on CSD susceptibility in mice. Thirty-two C57BL/6 mice (male, n = 16; female, n = 16) were intraperitoneally injected with either LCM (40 mg/kg) or saline prior to CSD induction. Potassium chloride (KCl) was administered to induce CSD, and CSD threshold, frequency, and propagation velocity were examined.

A single dose of LCM significantly reduced CSD frequency in female mice, suggesting a potential sex-dependent inhibitory effect on CSD. Further studies are warranted to explore the underlying mechanisms and assess the clinical potential of LCM as a preventive treatment for migraine.