Table 7.
Dose–response relations and corresponding ED50s for various effects observed over a 4-h period after challenge with RO-4-1284 (10 mg/kg, s.c.) in rats that received test compound simultaneously with RO-4-1284
| Effect | Dose of PQ-10 (mg/kg, s.c.) | ED50 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Time (h) | Criterion | 0.63 | 1.25 | 2.5 | 5.0 | 10 | 20 | 40 | (95% CL; mg/kg) |
| Reversal of sedation/passivity | |||||||||
| 1 | Absence (6.0%)1 | 0 | 0 | 5 | 4 | 5 | 3.6 (2.89–4.3) | ||
| 2 | Absence (4.0%)1 | 0 | 2 | 3 | 4 | 4 | 4.7 (2.38–7.0) | ||
| 3 | Absence (2.0%)1 | 1 | 2 | 3 | 2 | 2 | 7.1 (–) | ||
| 4 | Absence (16%)1 | 0 | 2 | 0 | 1 | 3 | 16.2 (–) | ||
| Reversal of catalepsy | |||||||||
| 2 | Score <2 (0.0%)1 | 0 | 0 | 1 | 3 | 5 | 8.2 (5.4–12.2) | ||
| 3 | Score <5 (2.0%)1 | 0 | 3 | 2 | 3 | 5 | 4.7 (2.91–7.6) | ||
| 4 | Score <5 (8.0%)1 | 0 | 1 | 0 | 3 | 4 | 10.7 (7.2–16.1) | ||
| Induction of excitation | |||||||||
| 1 | Presence (0.0%)1 | 0 | 0 | 0 | 0 | 3 | 19 (–) | ||
| 2 | Presence (0.0%)1 | 0 | 0 | 0 | 0 | 3 | 19 (–) | ||
| 3 | Presence (0.0%)1 | 0 | 0 | 1 | 0 | 3 | 19 (–) | ||
| 4 | Presence (0.0%)1 | 0 | 0 | 0 | 0 | 0 | >20 (–) | ||
The number of rats responding to the listed criterion is listed per dose level (n = 5 per dose group). Values representing more than 50% responders are formatted bold.
1
Percentage of false positives (solvent-pretreated rats responding to the criterion [n = 50]).