Motor toxicity (TD50) and anticonvulsant profile (ED50) of the neurosteroids in comparison with pregnenolone, DZP, PB and MK-801
| Compound | TD50 | COCAINE | NMDA (Seizures) | NMDA (Lethality) | PTZ |
|---|---|---|---|---|---|
| 3α,5α-P | 26.5 | 4.77 | >30.0 | 5.00 | 2.27 |
| (18.9–36.9) | (2.27–10.0) | (2.46–10.2) | (1.42–3.66) | ||
| 3α,5β-P | 28.7 | 3.94 | 19.1 | N.C. | 2.87 |
| (17.2–48.1) | (1.89–8.19) | (7.22–50.4) | (1.61–5.09) | ||
| Ganaxolone | 24.8 | 7.78 | >30.0 | 13.5 | 3.45 |
| (10.2–60.4) | (3.57–16.9) | (5.65–32.2) | (2.35–5.06) | ||
| Co 2-1068 | 51.8 | 13.1 | 7.32 | 6.61 | 6.17 |
| (31.5–85.1) | (4.82–35.7) | (1.97–27.2) | (0.89–49.1) | (3.47–11.0) | |
| Pregnenolone | >30.0 | >30.0 | >30.0 | >30.0 | >30.0 |
| DZP | 3.13 | >30.0 | 17.0 | 4.01 | 0.26 |
| (1.88–5.23) | (6.93–41.6) | (1.46–11.1) | (0.15–0.44) | ||
| PB | 84.5 | >170 | >170 | 43.7 | 6.04 |
| (66.9–107) | (32.3–59.0) | (3.26–11.2) | |||
| MK-801 | 0.078 | 0.15 | 0.062 | 0.062 | >0.30 |
| (0.05–0.12) | (0.11–0.21) | (0.029–0.13) | (0.029–0.13) |
The data represent the TD50 and ED50 values (with 95% confidence limits in parentheses) evaluated in the inverted screen test and the convulsant tests, respectively. The pretreatment times before a convulsant injection, as well as for the screen failure test, were 15 min for the neurosteroids and pregnenolone or 30 min for DZP, PB and MK-801. Cocaine, NMDA and PTZ were administered in the doses of 75, 200 and 70 mg/kg, respectively. N.C., Not calculated.