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| Discovery of the First Vitamin K Analogue as a Potential Treatment of Pharmacoresistant Seizures
Abstract
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.https://pubs.acs.org/doi/10.1021/acs.jmedchem.0c00168# New vitamin K-based drug shows promise against medication-resistant epilepsyhttps://web.musc.edu/about/news-center/202...-chou-july-2020 Edited by MEDICINAINFO - 28/8/2020, 14:30
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