Lacosamide: Novel action mechanisms and emerging targets in epilepsy and pain

SummaryThe new anticonvulsant Lacosamide (®Vimpat) selectively promotes slow inactivation of VGSCs, has a higher affinity for channels involved in sensory/pain transduction than CNS channels and was discovered in NIH in vivo screens. Click chemistry, the new crystal structure for VGSCs, and the profiling of related signalling pathways may further impact on drug discovery (and reveal the physiological process of slow inactivation). The surrogate binding target collapsin response mediator protein (CRMP-2) enhances lacosamide block at VGSCs. CRMP-2 also enhances N-type calcium channel (CaV2.2) expression and novel blocking peptides can reduce inflammatory pain in disease models. Mechanistic understanding and multi-disciplinary engagement is essential for cost-effective drug discovery in the quest to find safe, curative drugs in epilepsy and pain.