Table 7.
Chemically and electrically induced seizure studies in rats with PO and IP administration of cenobamate, YKP3090, and YKP1983 (NINDS study, n = 8–24/group).
| Seizure Model | Parameter | PO |
IP |
||||
|---|---|---|---|---|---|---|---|
| Cenobamate | YKP3090 | YKP1983 | Cenobamate | YKP3090 | YKP1983 | ||
| Minimum motor impairment | TD50 mg/kg (95% CI) | 50.7 (35.7–63.0) | <150 | 81.1 (61.1–112) | 38.9 (32.2–43.9) | 50.9 (33.1–67.8) | 53.3 (41.5–62.2) |
| SC PTZ 56.4 mg/kg or 68 mg/kga | ED50 mg/kg (95% CI) | Max. 40% protection at 25 | 8.14 (0.74–16.9) | Max. 33% protection at 12.5 | 13.6 (6.6–25.0) | 16.7 (14.8–18.7) | 19.3 (12.4–28.5) |
| PIb | NA | <18 | NA | 2.9 | 3.0 | 2.8 | |
| Hippocampal kindling | ED50 mg/kg (95% CI) | NT | NT | NT | 16.4 (12.7–20.2) | >50 (−) | Inactive at 30 |
| PIb | NA | NA | NA | 2.4 | <1 | NA | |
| MES | ED50 mg/kg (95% CI) | 1.9 (0.9–3.3) | 11.9 (8.5–15.0) | 2.9 (2.0–3.7) | 2.9 (1.9–3.8) | 26.1 (14.6–41.9) | 8.4 (6.9–9.8) |
| PIb | 27 | <13 | 28 | 14 | 2.0 | 6.4 | |
CI, confidence interval; ED50, median effective dose; IP, intraperitoneal; MES, maximal electroshock seizures; NA, not applicable/available; NINDS, National Institute of Neurological Disorders and Stroke; NT, not tested; PI, protective index; PO, oral; PTZ, pentylenetetrazol; SC, subcutaneous; TD50, median neurotoxic dose.
a56.4 mg/kg for rats sourced from Simonsen Laboratories, Inc. and 68 mg/kg for rats sourced from Charles River Laboratories.
bProtective index calculation TD50/ED50. TD50 based on minimal motor impairment.