TABLE 5.
ED50 values (95% CIs) for the discriminative-stimulus, rate-decreasing, and antinociceptive effects of various compounds in rats trained to discriminate 3.2 mg/kg morphine as shown in Figs. 3–10 and Supplemental Figs. 5–7
The sample sizes are described in each figure legend. Each value is a combination of females and males unless otherwise noted. For each training drug, potency ratios (95% CIs) are calculated by dividing the ED50 values for producing rate-decreasing or antinociceptive effects by the ED50 values for producing discriminative-stimulus effects.
| Test Drug | ED50 (95% CIs) | Potency Ratio | |||
|---|---|---|---|---|---|
| Discrimination | Response Rate | Maximum Possible Effect | Rate-Decreasing/Discrimination | Antinociceptive/Discrimination | |
| 7-Hydroxymitragynine | 0.275 (0.0768–0.411) | 4.73 (3.25–6.35) | 10.6 (9.26–12.3) | 17.2 (7.91–82.7) | 38.5 (22.5–160) |
| 7-Hydroxymitragynine + 0.032 mg/kg naltrexone | 0.670 (0.602–0.744) | 6.09 (4.78–7.53) | ND [≤ −2.81% (2.03%) at 32 mg/kg]a | 9.09 (6.42–12.5) | Not applicable |
| Buprenorphine | 0.0844 (0.0456–0.122) | 0.343 (0.249–0.533) | ND [≤ −2.81% (2.03%) at 0.56 mg/kg]a | 4.06 (2.04–11.7) | Not applicable |
| Fentanyl | 0.0220 (0.0111–0.0318) | 0.173 (0.150–0.202) | 0.139 (0.112–0.166) | 7.86 (4.72–18.2) | 6.32 (3.52–15.0) |
| Mitragynine | 29.6 (18.8–55.9) | 45.7 (36.4–64.1) | ND [≤7.01% (6.50%) at 5.6 mg/kg]a | 1.54 (0.651–3.41) | Not applicable |
| Morphine | 1.85 (1.54–2.20)b, 1.60 (1.30–1.91)c | 13.7 (10.6–16.8)b, 21.3 (16.8–26.2)c | 35.2 (32.6–38.1)b, 33.4 (30.9–36.4)c | 7.41 (4.82–10.9)b, 13.3 (8.80–20.2)c | 19.0 (21.2–24.7)b, 20.9 (16.2–28.0)c |
| Morphine + 0.032 mg/kg naltrexone | 15.2 (12.7–17.9) | 35.4 (28.2–47.2) | ND [≤3.35% (1.92%) at 56 mg/kg]d | 2.33 (1.58–3.72) | Not applicable |
| Morphine + 1.78 mg/kg Nalbuphine | 0.335 (0.202–0.444) | 26.0 (22.4–30.3) | ND [≤27.4% (4.95%) at 56 mg/kg]d | 77.6 (50.5–150) | Not applicable |
| Morphine + 5.6 mg/kg Mitragynine | 0.478 (0.265–0.503) | 11.7 (9.33–14.2) | ND [≤40.6% (6.92%) at 56 mg/kg]d | 24.5 (18.6–53.6) | Not applicable |
| Nalbuphine | 7.29 (2.33–11.0) | 81.3 (68.9–96.8) | ND [≤2.86% (5.49%) at 178 mg/kg]e | 11.2 (6.26–41.5) | Not applicable |
| SNC 80 | ND [≤34.3% (11.3%) at 56 mg/kg]e | ND [≤51.2% (13.2%) at 100 mg/kg]e | ND [≤8.63% (5.47%) at 100 mg/kg]e | Not applicable | Not applicable |
| U69,593 | 2.29 (1.64–4.37) | 2.30 (1.85–2.77) | 5.05 (4.12–6.76) | 1.00 (0.423–0.634) | 2.21 (0.943–4.12) |
a
Due to lethality.
b
First assessment.
c
Reassessment.
d
Due to an adverse reaction (scratching behavior).
e
Due to insolubility in the chosen vehicle.