Table 2.
Correlation of between neurosteroid activation of tonic inhibition and seizure protection in in mouse 6-Hz model.
Neurosteroid | Tonic Currents | Seizure Protection ED50 (mg/kg)*** | |
---|---|---|---|
E1 μM (pA)* | EF(2-fold GABA) (nM)** | ||
Brexanolone (AP) | 100.6 | 80 | 4.2 (2.7–5.8) |
Ganaxolone | 64.0 | 290 | 1.5 (1.3–1.7) |
Pregnanolone | 44.4 | 780 | 7.7 (6.6–8.8) |
Isopregnanolone | 15.3 | >10000 | > 100 |
THDOC | 66.6 | 410 | 5.0 (2.6–7.4) |
Alfaxolone | 40.9 | 990 | 8.8 (6.1–11.4) |
ORG-20599 | 86.4 | 120 | 18.6 (16.6–20.6) |
Androstanediol | 33.2 | 1710 | 44.0 (30.2–58.8) |
E1 μM values represent the mean normalized tonic current responses of drug at 1 μM concentration co-applied with 1 μM GABA. GABA 1 μM tonic current: 0.66 ± 0.22 pA/pF, 19.6 pA.
EF values represent the effective functional concentration of drug (nM) required to double or triple the 1 μM GABA response.
ED50 values represent the dose in milligrams per kilogram that protected 50% of animals in the 6-Hz seizure stimulation test. 95% confidence intervals are listed in parenthesis, according to a normal distribution.