As seen in many of these research summaries, models that reliably mimic human Dravet syndrome, such as engineered mice and zebrafish, allow labs to try out various potential drugs in a quick and safe manner. In this study, the researchers used a Dravet mouse model to test the efficacy of donepezil (a.k.a. “Aricept”), an FDA-approved drug used to treat dementia. They found that donepezil conferred protection against electrically induced seizures in the Dravet syndrome mouse model (although not against heat-induced seizures).

The primary action of donepezil is to inhibit an enzyme called acetylcholinesterase (it’s an “AchEI”), and thereby raise levels of a key brain neurotransmitter – this presents an unclear connection to epilepsy. However, it is not uncommon for compounds to have multiple activities, and the researchers do note that the anti-seizure effect of donepezil was not well-correlated to its AchEI activity; and that it may have been working through GABA receptors (as many Dravet syndrome treatments do). This study suggests it might be worth checking other AchEI’s as possible Dravet syndrome therapeutics.

Wong, J.C., Thelin, J.T., and Escayg, A. Donepezil increases resistance to induced seizures in a mouse model of Dravet syndrome. Annals of Clinical and Translational Neurology 2019; 6(8): 1566–1571. doi: 10.1002/acn3.50848.