At the Society of Toxicology 58th Annual Meeting and ToxExpo from March 10th to 14th at the Baltimore Convention Center, Dr Michael Morton of ApconiX will be giving a talk as part of the workshop “Can we panelize seizure?”. On Wednesday March 13th 9:30am – 10:00am in the Convention Center Ballroom III. An Innovations in Applied Toxicology designated session.
Using Ion Channels to Panelize Seizure: Where Are We Up To?
Authors: M. Morton. ApconiX, Alderley Edge, United Kingdom. Sponsor: J. Pierson
There is clear evidence for the involvement of ion channels in seizure. Genetic studies have pointed to a role for voltage-gated sodium and potassium channels and the ligand-gated ion channels, GABA-A and nicotinic acetylcholine receptors. Pharmacologically, a number of ion channel modulators are known to be seizurogenic such as Chlorpromazine. Should we therefore be looking to screen compounds in early discovery against a panel of ion channels, and what would this panel look like? Ion channel screening against a panel of ion channels has been successfully employed for decades to reduce cardiovascular safety liability. Routine screening against the cardiac potassium, sodium and calcium channels, and optimization of medicinal chemistry away from these liabilities, has reduced the number of drug withdrawals due to hERG/QT prolongation. Coupled with an informatics approach, screening for cardiovascular liability in entering a new paradigm with the advent of the comprehensive in vitro proarrhythmic assessment (CiPA). Can the same approach be applied to reducing seizure liability? The challenges include the complexity of CNS pharmacology along with the more practical challenges of identifying which channels to screen. Which is the best cellular reagent to use: recombinant cell lines expressing an individual ion channel, or a more physiologically relevant substrate such as stem-cell derived neurones? The current state of play including lessons learned from the hERG/CIPA experience will be presented and a screening strategy hypothesized.
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