Table 1.
VsEP latency, amplitude, and threshold before and after different doses of XE991 and saline
| XE991 |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| VsEPs | 50 mg/kg (5, 3) | 25 mg/kg (6) | 12.5 mg/kg (5) | 5 mg/kg (6) | 3.5 mg/kg (6) | 2.5 mg/kg (5) | 1 mg/kg (5) | 0.5 mg/kg (5) | 0.05 mg/kg (5) | Saline (5) |
| Latency, µs | ||||||||||
| P1 | ||||||||||
| Baseline | 1,375 ± 49 | 1,336 ± 55 | 1,354 ± 24 | 1,327 ± 58 | 1,347 ± 41 | 1,330 ± 68 | 1,356 ± 34 | 1,325 ± 54 | 1,264 ± 56 | 1,337 ± 68 |
| 0–20 min | 1,531 ± 101 | 1,412 ± 41 | 1,459 ± 43 | 1,371 ± 66 | 1,353 ± 59 | 1,306 ± 65 | 1,313 ± 40 | 1,315 ± 55 | 1,258 ± 56 | 1,338 ± 78 |
| 25–40 min | 1,655 ± 51 | 1,580 ± 36 | 1,627 ± 24 | 1,512 ± 77 | 1,449 ± 73 | 1,318 ± 58 | 1,275 ± 38 | 1,276 ± 50 | 1,245 ± 52 | 1,338 ± 83 |
| 45–60 min | 1,640 ± 59 | 1,585 ± 38 | 1,632 ± 26 | 1,519 ± 85 | 1,462 ± 45 | 1,351 ± 60 | 1,268 ± 30 | 1,265 ± 40 | 1,238 ± 61 | 1,326 ± 84 |
| N1 | ||||||||||
| Baseline | 1,701 ± 82 | 1,629 ± 59 | 1,662 ± 18 | 1,610 ± 82 | 1,651 ± 48 | 1,624 ± 55 | 1,639 ± 27 | 1,626 ± 47 | 1,572 ± 30 | 1,639 ± 791 |
| 0–20 min | 1,856 ± 144 | 1,706 ± 39 | 1,768 ± 53 | 1,662 ± 89 | 1,643 ± 62 | 1,590 ± 61 | 1,599 ± 19 | 1,604 ± 50 | 1,567 ± 30 | 1,643 ± 90 |
| 25–40 min | 1,957 ± 23 | 1,939 ± 65 | 1,959 ± 28 | 1,844 ± 88 | 1,773 ± 51 | 1,585 ± 70 | 1,569 ± 35 | 1,562 ± 41 | 1,536 ± 45 | 1,637 ± 97 |
| 45–60 min | 1,943 ± 46 | 1,935 ± 60 | 1,963 ± 23 | 1,848 ± 84 | 1,780 ± 45 | 1,631 ± 66 | 1,566 ± 47 | 1,550 ± 36 | 1,524 ± 44 | 1,625 ± 95 |
| P2ab | ||||||||||
| Baseline | 2,069 ± 41 | 1,973 ± 81 | 2,090 ± 41 | 2,072 ± 86 | 2,023 ± 72 | 2,032 ± 67 | 2,046 ± 64 | 1,988 ± 24 | 1,915 ± 38 | 2,015 ± 80 |
| 0–20 min | 2,358 ± 110 | 2,164 ± 94 | 2,265 ± 84 | 2,188 ± 104 | 2,133 ± 71 | 2,047 ± 83 | 2,060 ± 62 | 1,966 ± 44 | 1,919 ± 31 | 2,008 ± 84 |
| 25–40 min | 2,572 ± 33 | 2,526 ± 204 | 2,511 ± 164 | 2,465 ± 101 | 2,357 ± 75 | 2,161 ± 62 | 2,164 ± 48 | 2,006 ± 56 | 1,926 ± 35 | 2,003 ± 92 |
| 45–60 min | 2,572 ± 24 | 2,536 ± 183 | 2,523 ± 167 | 2,457 ± 78 | 2,381 ± 94 | 2,257 ± 89 | 2,207 ± 39 | 2,042 ± 34 | 1,935 ± 36 | 1,999 ± 96 |
| Amplitude, µV | ||||||||||
| P1N1 | ||||||||||
| Baseline | 0.93 ± 0.22 | 0.81 ± 0.15 | 1.01 ± 0.29 | 0.97 ± 0.15 | 0.97 ± 0.18 | 1.01 ± 0.21 | 0.89 ± 0.24 | 1.02 ± 0.17 | 0.89 ± 0.16 | 0.84 ± 0.16 |
| 0–20 min | 0.63 ± 0.17 | 0.69 ± 0.14 | 0.79 ± 0.14 | 0.86 ± 0.14 | 0.96 ± 0.12 | 1.08 ± 0.18 | 0.94 ± 0.26 | 1.05 ± 0.14 | 0.91 ± 0.22 | 0.86 ± 0.17 |
| 25–40 min | 0.33 ± 0.06 | 0.38 ± 0.13 | 0.50 ± 0.13 | 0.61 ± 0.17 | 0.80 ± 0.14 | 1.18 ± 0.23 | 1.06 ± 0.32 | 1.12 ± 0.14 | 0.96 ± 0.19 | 0.87 ± 0.15 |
| 45–60 min | 0.31 ± 0.06 | 0.45 ± 0.15 | 0.56 ± 0.14 | 0.31 ± 0.06 | 0.87 ± 0.11 | 1.15 ± 0.23 | 1.11 ± 0.26 | 1.16 ± 0.21 | 1.03 ± 0.22 | 0.86 ± 0.20 |
| P2abN1 | ||||||||||
| Baseline | 0.68 ± 0.23 | 0.65 ± 0.15 | 0.94 ± 0.21 | 0.91 ± 0.33 | 0.91 ± 0.20 | 0.74 ± 0.17 | 0.79 ± 0.12 | 0.83 ± 0.18 | 0.78 ± 0.23 | 1.10 ± 0.46 |
| 0–20 min | 0.52 ± 0.22 | 0.66 ± 0.12 | 0.75 ± 0.33 | 0.99 ± 0.42 | 1.07 ± 0.16 | 0.89 ± 0.14 | 1.05 ± 0.28 | 0.96 ± 0.12 | 0.85 ± 0.28 | 1.06 ± 0.45 |
| 25–40 min | 0.52 ± 0.24 | 0.46 ± 0.24 | 0.31 ± 0.21 | 0.62 ± 0.27 | 0.97 ± 0.27 | 1.03 ± 0.17 | 1.27 ± 0.32 | 1.03 ± 0.16 | 0.85 ± 0.27 | 1.05 ± 0.51 |
| 45–60 min | 0.52 ± 0.27 | 0.43 ± 0.21 | 0.31 ± 0.16 | 0.58 ± 0.27 | 0.95 ± 0.29 | 1.14 ± 0.18 | 1.27 ± 0.34 | 1.04 ± 0.16 | 0.95 ± 0.28 | 1.08 ± 0.49 |
| Threshold, dB re:1 g/ms | ||||||||||
| Baseline | −9.9 ± 1.3 | −10.5 ± 1.9 | −11.1 ± 1.3 | −10.5 ± 0.0 | −10.0 ± 1.2 | −9.3 ± 1.6 | −11.1 ± 1.3 | −9.9 ± 2.5 | −8.7 ± 1.6 | −9.9 ± 1.3 |
| 0–20 min | −3.5 ± 1.7 | −3.0 ± 4.1 | −3.3 ± 1.6 | −5.0 ± 2.3 | −8.5 ± 3.6 | −11.1 ± 1.3 | −12.3 ± 1.6 | −10.5 ± 2.1 | −9.3 ± 1.6 | −9.3 ± 1.6 |
| 25–40 min | −1.5 ± 0.0 | −4.0 ± 2.3 | −3.3 ± 2.7 | −5.0 ± 2.3 | −7.0 ± 2.3 | −9.9 ± 1.3 | −11.7 ± 2.78 | −11.1 ± 2.5 | −10.5 ± 0.0 | −9.9 ± 1.3 |
| 45–60 min | −1.5 ± 3.0 | −4.0 ± 3.0 | −3.9 ± 3.3 | −6.0 ± 1.6 | −7.5 ± 1.9 | −9.3 ± 1.6 | −12.3 ± 1.6 | −12.3 ± 1.6 | −8.7 ± 1.6 | −9.3 ± 1.6 |
Values are means ± SD of vestibular response (VsEP) latency, amplitude, and threshold over a period of 60 min following a 20-min stable baseline period for each of 9 different XE991 doses and saline; sample size (n) is indicated in parentheses for each group. Each 20-min period was an average of 4–5 consecutive measurements ~5 min apart. In the 50 mg/kg dose group, responses were essentially eliminated following XE991 administration in 2 animals. All mice were anesthetized with urethane-xylazine and monitored with rectal and brain temperature probes throughout the experiments. Stimulus level was +6 dB re: 1.0 g/ms for latency and amplitude measurements. The latency for P2 is represented as P2ab = (P2a + P2b)/2, which defined a composite value for P2 when in bifed form of P2a and P2b.