Diphenytoin, riluzole and lidocaine: three sodium channel blockers, with different mechanisms of action, decrease
Lihong Diao1, Jennifer L Hellier, Jessica Uskert-Newsom
1University of Colorado Anschutz Medical Campus, Mailstop 8105, PO Box 6511, Aurora, CO 80045, USA.
Neuropharmacology
|May 28, 2013
Summary
Novel sodium channel blockers, diphenytoin and riluzole, reduced epileptic activity in brain slices. This study highlights a new method for screening epilepsy drugs by measuring network excitability.
Area of Science:
- Neuroscience
- Pharmacology
- Epilepsy Research
Background:
- Epilepsy affects 1-2% of the population with recurrent seizures.
- Temporal lobe epilepsy (TLE) is the most common acquired form.
- Drug-resistant TLE necessitates novel therapeutic targets.
Purpose of the Study:
- To investigate alterations in network excitability using an in-vitro CA3 burst preparation.
- To identify compounds that decrease epileptiform activity.
Main Methods:
- Utilized an in-vitro CA3 burst preparation.
- Examined changes in interburst intervals.
- Applied sodium channel blockers: diphenytoin, riluzole, and lidocaine.
Main Results:
- Diphenytoin, riluzole, and lidocaine slowed spontaneous CA3 bursts, decreasing epileptiform activity.
- Diphenytoin and riluzole showed persistent effects after washout.
- Lidocaine's effect was transient, returning bursting to baseline post-washout.
Conclusions:
- The CA3 burst preparation is an effective platform for screening compounds that reduce network excitability.
- This model facilitates the identification of potential new epilepsy therapies.
- Diphenytoin and riluzole demonstrate promise for further in-vivo studies.
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