Table 9.
Effect of cenobamate, YKP3090, and YKP1983 on the rotarod test and minimal motor impairment in rats (multiple studies).
| Study Type (STUDY) | Test Compound | Route & Dose | N per dose tested | Time of Test (post-dose in h) | TD50 mg/kg (95% CI) |
|---|---|---|---|---|---|
| Rotarod test (Q) | Cenobamate | PO 150, 200, 250 mg/kg | 8 | 4 | 195.7 (158.0–242.5) |
| Rotarod test (R) | Cenobamate | PO 100, 150, 200, 250 mg/kg | 6 | 1 2 |
347.5 (146.7–823.2) 244.4 (88.2–677.2) |
| Rotarod test (S) | Cenobamate | PO 10, 30, 100, 250 mg/kg (3 batches 1401-1401-07-001; 1401-1401-05-501; DIT040503) | 6 | 0.5 to 5 | 101.6 (27.9–220.1) |
| 6 | 104.1 (40.0–204.4) | ||||
| 6 | 100.4 (−2.0-305.9) | ||||
| Minimal motor impairment (NINDS) | Cenobamate | PO 25, 50, 75, 100 mg/kg | 8 | 1 | 50.7 (35.7–63.0) |
| YKP3090 | PO 50, 100, 150 mg/kg | 8 | 1 | <150a (N/A) | |
| YKP1983 | PO 50, 75, 120 mg/kg | 8 | 1 | 81.1 (61.1–112) | |
| Cenobamate | IP 15, 30, 40, 50, 60 mg/kg | 8 | 0.25 | 38.9 (32.2–43.9) | |
| YKP3090 | IP 10, 20, 25, 50,75, 100 mg/kg | 8 | 0.5 | 50.9 (33.1–67.8) | |
| YKP1983 | IP 2, 7.5, 8, 15, 30, 50, 60, 73 mg/kg | 4–12 | 0.5 | 53.3 (41.5–62.2) |
aTD50 could not be calculated but estimated to be 150 mg/kg PO or less; h, hours; IP, intraperitoneal; NINDS, National Institute of Neurological Disorders and Stroke; PO, oral; RT, rotarod test; TD50, median neurotoxic dose.