Discovery of the First Vitamin K Analogue as a Potential Treatment of Pharmacoresistant Seizures

Despite
the availability of more than 25 antiseizure drugs on the
market, approximately 30% of patients with epilepsy still suffer from
seizures. Thus, the epilepsy therapy market has a great need for a
breakthrough drug that will aid pharmacoresistant patients. In our
previous study, we discovered a vitamin K analogue, 2h, which displayed modest antiseizure activity in zebrafish and mouse
seizure models. However, there are limitations to this compound due
to its pharmacokinetic profile. In this study, we develop a new series
of vitamin K analogues by modifying the structure of 2h. Among these, compound 3d shows full protection in
a rodent pharmacoresistant seizure model with limited rotarod motor
toxicity and favorable pharmacokinetic properties. Furthermore, the
brain/plasma concentration ratio of 3d indicates its
excellent permeability into the brain. The resulting data shows that 3d can be further developed as a potential antiseizure drug
in the clinic.