Table 4.
Mean ED50 values, dose ratios and respective 95% CL for rate-decreasing effects of midazolam, pentobarbital and morphine before, during and after daily flunitrazepam treatment. During daily treatment with two injections of 1 mg/kg of flunitrazepam, dose-effect curves were determined under two different conditions: when the treatment dose of flunitrazepam was last administered 1 hr before sessions and when the treatment dose flunitrazepam was last administered 25 hr before sessions with flunitrazepam vehicle administered before sessions.
| ED50 (mg/kg) | Dose ratioa | |||
|---|---|---|---|---|
| Value | 95% CL | Value | 95% CL | |
| Midazolam | ||||
| Before | 0.58 | 0.34-0.81 | -- | |
| During 2 × 1 mg/kg flunitrazepam | ||||
| 1 hr | 11.64* | 5.48-17.80 | 22.95 | 8.01-37.8 |
| 25 hr | 6.65* | 0.27-13.02 | 10.53 | 1.52-19.54 |
| After | 1.91 | 0.14-3.69 | 3.89 | -0.48-8.27 |
| Pentobarbital | ||||
| Before | 6.50 | 5.49-7.50 | -- | |
| During 2 × 1 mg/kg flunitrazepam | ||||
| 1 hr | 8.47 | 4.66-12.27 | 1.33 | 0.70-1.95 |
| 25 hr | 8.71 | 3.20-14.22 | 1.37 | 0.48-2.25 |
| After | 9.38* | 6.71-12.04 | 1.47 | 1.04-1.91 |
| Morphine | ||||
| Before | 4.05 | 2.37-5.72 | -- | |
| During 2 × 1 mg/kg flunitrazepam | ||||
| 1 hr | 5.00 | 0.11-9.88 | 1.35 | 0.02-2.67 |
| 25 hr | 1.10* | -0.03-2.23 | 0.27 | 0.08-0.46 |
| After | 1.76 | 0.60-2.92 | 0.60 | 0.15-1.04 |
a
Dose ratios are relative to ED50 values determined before treatment.
*
indicates a significant difference from ED50 determined before daily flunitrazepam treatment