Table 4.
VsEP response latencies in the diazepam and BPEW vehicle progressive multiple dose (PMD) protocol with and without brain temperature controlled. VsEP latencies (µs) at + 6 dB re:1.0 g/ms were obtained over a period of 80 min following a 20-min stable baseline period. Data were measured from mice where brain and rectal temperatures were controlled [“Brain + Rectal”] as well as from mice where only rectal temperature was controlled [”Rectal Only”]. Four incremental doses of diazepam were given (post dose 1 “PD1”: 6 mg/kg; post dose 2 “PD2”: 12 mg/kg; post dose 3 “PD3”: 24 mg/kg; post dose 4 “PD4”: 48 mg/kg). Each time period (20 min) was characterized by averaging 4 to 5 consecutive 5-min measurements as a 20-min period. Data reflect mean ± standard deviation. “Rectal only” animals were anesthetized with ketamine/xylazine whereas “Brain + Rectal” animals were anesthetized with urethane/xylazine. Brain temperatures were held at 36.0 ± 0.2 °C and rectal at 37.0 ± 0.2 °C. BPEW vehicle: 1.4% benzyl alcohol, 38.5% propylene glycol, 12.7% ethyl alcohol and 48% water. In the “Injection” column, the parentheses “(n)” reflect the sample size, which remained constant over the entire study
| VsEP parameters | Temperatures | Injection (n) | Baseline | PD1 (1–20 min) | PD2 (21–40 min) | PD3 (41–60 min) | PD4 (61–80 min) | |
|---|---|---|---|---|---|---|---|---|
| Latency (µs) | P1 | Brain + Rectal | Diazepam (10) | 1223 ± 31 | 1245 ± 42 | 1264 ± 46 | 1289 ± 48 | 1295 ± 41 |
| BPEW (6) | 1222 ± 32 | 1220 ± 29 | 1224 ± 30 | 1223 ± 28 | 1224 ± 32 | |||
| Rectal Only | Diazepam (10) | 1380 ± 106 | 1357 ± 112 | 1367 ± 121 | 1405 ± 129 | 1473 ± 134 | ||
| BPEW (10) | 1377 ± 88 | 1363 ± 92 | 1374 ± 112 | 1385 ± 114 | 1398 ± 117 | |||
| N1 | Brain + Rectal | Diazepam (10) | 1487 ± 40 | 1514 ± 45 | 1533 ± 46 | 1559 ± 48 | 1574 ± 42 | |
| BPEW (6) | 1520 ± 55 | 1522 ± 59 | 1520 ± 58 | 1521 ± 60 | 1521 ± 63 | |||
| Rectal Only | Diazepam (10) | 1694 ± 119 | 1667 ± 123 | 1673 ± 128 | 1724 ± 141 | 1808 ± 153 | ||
| BPEW (10) | 1687 ± 94 | 1674 ± 103 | 1686 ± 126 | 1704 ± 136 | 1723 ± 141 | |||
| P2 | Brain + Rectal | Diazepam (10) | 1905 ± 52 | 1937 ± 72 | 1985 ± 89 | 2018 ± 81 | 2062 ± 758 | |
| BPEW (6) | 1906 ± 51 | 1913 ± 42 | 1899 ± 58 | 1904 ± 62 | 1913 ± 55 | |||
| Rectal Only | Diazepam (10) | 2170 ± 140 | 2140 ± 148 | 2167 ± 160 | 2231 ± 175 | 2334 ± 197 | ||
| BPEW (10) | 2169 ± 124 | 2147 ± 135 | 2157 ± 140 | 2186 ± 146 | 2208 ± 143 | |||