Table 2.
Concentration-Response Summary of ASD effects on RED duration, frequency, and amplitude in layer II of the mEC.
| Target Class | ASD | Duration EC50 (µM) Predicted Max (%) |
Frequency EC50 (µM) Predicted Max (%) |
Amplitude EC50 (µM) Predicted Max (%) |
EC50 / Ave. human plasma conc. |
|---|---|---|---|---|---|
| Na+ | Carbamazepine | 25.8 0% |
128.7 0% |
153.6 227.1% |
0.81 |
| Na+ | Eslicarbazepine | 299.2 0% |
91.9 0% |
631.9 0% |
1.43 |
| Na+ | Rufinamide | - | 276.0 31.1% |
- | 1.88 |
| Na+ | Phenytoin | 356.7 0% |
127.8 0% |
- | 2.15 |
| Na+ / h-current | Lamotrigine | 79.3 0% |
84.0 0% |
787.5 0% |
2.32 |
| Na+ / slow inactivation | Lacosamide | 318.1 8.9% |
78.6 35.3% |
- | 2.62 |
| K+ | Ezogabine | 2.8 0% |
11.8 0% |
21.4 0% |
2.80 |
| GABA / reuptake | Tiagabine | 0.4 42.5% |
472.7 0% |
- | 2.50 |
| GABA / barbiturate | Phenobarbital | 477.5 0% |
270.1 0% |
- | 3.58 |
| GABA-T inhibitor | Vigabatrin | 2767.0 289.1% |
1909.0 0% |
- | 13.40 |
| GABA / 1,5- benzodiazepine |
Clobazam | - | 79.1 42.2% |
- | 39.55 |
| GABA / 1,4- benzodiazepine |
Midazolam | 21.3 165% |
112.3 0% |
- | 42.60 |
| GABA / mixed | Stiripentol | - | - | - | - |
| NKCC1 | Bumetanide | - | 0.9 82.0% |
- | 0.15 |
| Ca2+ | Ethosuximide | 1496.0 180.0% |
290.2 88.9% |
- | 0.59 |
| Mixed | Topiramate | 38.5 151.0% |
26.9 73.0% |
- | 0.73 |
| SV2A | Levetiracetam | - | - | - | - |
| Mixed | Valproate | - | - | - | - |
| Mixed | Felbamate | - | - | - | - |
| Ca2+ | Gabapentin | - | - | - | - |
“-” = Not Calculable. EC50: Half-maximum Effective Concentration. Predicted Max (%): computationally derived concentration-response curve plateaus. Average (Ave.) plasma concentrations were adapted from Bialer, M., Twyman, R. E. & White, H. S. Epilepsy Behav 5, 866–872 (2004)37, Löscher, W. Epilepsia 48, 1245–1258 (2007),38 Krasowski, M. D. Pharmaceuticals 3, 1909–1935 (2010)39, Rey, E., Tréluyer, J. M. & Pons, G. Clin Pharmacokinet 36, 409–424 (1999)40, and Gunthorpe, M. J., Large, C. H. & Sankar, R. Epilepsia 53, 412–424 (2012)26.