Abstracts

Rationale: Antiepileptic drugs (AEDs) are both the first line and last resort for prevention of seizures in epilepsy. Patients with refractory epilepsy are often treated with multiple AEDs; however, the abundance of available AEDs make it difficult to implement rational polytherapy. In order to do so, clinicians must have a comprehensive understanding of their mechanisms of action, which in most cases are directly characterized through patch clamp electrophysiology recordings. Additionally, incorporating patch clamp data into computer models may allow prediction of effective antiepileptic medications for a given channelopathy. To these ends, we carried out a systematic review of studies that quantitatively characterized the effects of antiepileptic drugs on ion channels implicated in epilepsy using patch clamp electrophysiology techniques. Methods: The PubMed database was searched without date restriction using the term “patch clamp” paired with the name of each of 24 FDA approved antiepileptic drugs. We included studies that used patch clamp techniques to study either channels expressed in neurons directly, channels expressed in neuronal tissue that were transfected into host cells, or certain model systems based on neuronal tumors. Studies were excluded if they used native tissues outside the nervous system, did not report quantitative electrophysiology data for the AED that was listed in the search, or did not report data for AED effects in normally functioning tissue or channels. In order to further narrow our search results to a manageable size, we prioritized data from studies with transfected cDNA or cells from cerebral cortex, and excluded studies from peripheral nervous system if this data were available for a drug receptor combination. Results: 1124 abstracts describing effects of AEDs on channels (872 unique abstracts) were obtained in the initial search, which was reduced to 300 studies (213 unique) after the application of inclusion and exclusion criteria. 238 studies utilized native tissue, 38 studies utilized transfection of cDNA into host cells such as HEK239 or xenopus oocytes, and 25 utilized neuroblastoma cell lines. Rats (209 studies) and mice (61 studies) were native tissue models most commonly employed; 38 studies used human tissue or cDNA. Studies described effects of AEDs on 27 different ion channels. Qualitative effects of AEDs on channels are summarized visually in figure 1, quantitative results are not pictured. Conclusions: Patch clamp electrophysiology has quantitatively characterized the effects of AEDs on many channels, although many combinations remain untested. Certain mechanisms (such as medications acting on SVA2) cannot be directly tested with patch clamp electrophysiology. Many medications act on multiple channels, posing a challenge to clinicians seeking to use medications with complimentary mechanisms of action. These difficulties highlight the potential utility for computer models that could predict the effective combinations of AEDs. It is our hope that this data summarized in this review will prove a useful resource for computational neurologists and clinicians alike. Funding: none