Intrathecal d-methadone prevents the development of tolerance to the analgesic effect of morphine
| Treatment | Morphine | ||
|---|---|---|---|
| Day | ED50(i.t.) | 95% Confidence Interval | |
| μg/rat | |||
| Saline + morphine | 1 | 1.0 | 0.5–1.8 |
| Saline + morphine | 5 | 37.72-a | 25.9–56.7 |
| d-Methadone + morphine | 1 | 3.1 | 1.4–6.6 |
| d-Methadone + morphine | 5 | 1.42-a | 0.7–2.7 |
Tolerance was produced by the administration of escalating i.t. doses of morphine 3 times per day at 10 μg/rat on day 1, 20 μg/rat on day 2, and 40 μg/rat on day 3. The dose of d-methadone was 160 μg/rat. On day 5, the ED50 values for morphine, with their 95% confidence interval, were determined via cumulative dose-response assessment.
↵2-a Significantly different (P < .05) from day 1 saline + morphine group.
2-b Significantly different (P < .05) from day 5 saline + morphine group.