pKi values and Hill slopes of selective synaptic vesicle protein (SV)2A ligands and diazepam for sites labeled with 0.9 nM [3H]padsevonil on recombinant human SV2A/B/C and on human and rat cortex at 37°C. Data are presented as mean ± S.D. (n = 3–10) and were obtained from nonlinear regression analysis of untransformed raw data using a sigmoidal dose-response model with variable slope. Missing values could not be calculated because of incomplete competition curves as a result of compound solubility limits.
| Levetiracetam | Brivaracetam | UCB30889 | Padsevonil | Diazepam | |
|---|---|---|---|---|---|
| pKi | |||||
| SV2A | 5.2 ± 0.1 | 6.6 ± 0.1 | 6.7 ± 0.2 | 8.5 ± 0.1 | <5 |
| SV2B | 3.1 ± 0.04 | <4 | <4 | 7.9 ± 0.1 | <5 |
| SV2C | 3.2 ± 0.1 | 4.2 ± 0.1 | 4.8 ± 0.2 | 8.5 ± 0.2 | 5.6 ± 0.1 |
| Human cortex | 5.3 ± 0.3 | 6.4 ± 0.2 | 6.7 ± 0.2 | 8.7 ± 0.1 | 5.9 ± 0.4 |
| Rat cortex | 5.0 ± 0.1 | 6.4 ± 0.1 | 6.6 ± 0.2 | 8.7 ± 0.1 | <5 |
| Hill slope | |||||
| Human cortex | −0.71 ± 0.03 | −0.68 ± 0.05 | −0.74 ± 0.12 | −0.99 ± 0.21 | ND |
| Rat cortex | −0.76 ± 0.03 | −0.74 ± 0.26 | −0.79 ± 0.15 | −0.94 ± 0.13 | ND |
ND, not determined.