A1362WM

A1362WM is a selective positive allosteric modulator (potentiator) of the voltage-gated sodium channel subunit alpha Nav1.1 (SCN1A). Developed by Lundbeck, the compound is designed to increase the excitability of fast-spiking interneurons (FSIs), such as parvalbumin-positive interneurons, to restore the balance of excitation and inhibition in the brain. In preclinical studies, A1362WM demonstrated selective potentiation of Nav1.1 channels over other Nav1.x subtypes and increased the excitability of putative FSIs in hippocampal slices ex vivo. However, in a mouse model of hyperthermia-induced seizures in Dravet syndrome, A1362WM at doses up to 300 mg/kg did not significantly affect the latency to seizures.