TABLE 2.
ED50 values (95% CIs in parentheses) for the discriminative stimulus, rate-decreasing, and antinociceptive effects for various compounds in rats trained to discriminate 32 mg/kg mitragynine or 3.2 mg/kg morphine from their vehicle as shown in Figs. 2 and 3
The sample sizes are described in each figure legend. Each value is for a combination of females with males unless described. In each training drug, potency ratios per compound (95% CIs in parentheses) are calculated as a division of the ED50 values for the rate-decreasing or antinociceptive effects from those for the discriminative-stimulus effects. Significant differences are italicized.
| Test Drug | ED50 (95% CIs) | Potency Ratio (95% CIs) | |||
|---|---|---|---|---|---|
| Discriminative Stimulus | Response Rate | Maximum Possible Effect | Rate-Decreasing / Discriminative Stimulus | Antinociceptive / Discriminative Stimulus | |
| Rats Trained to Discriminate an Injection of 32 mg/kg Mitragynine from Its Vehicle | |||||
| Mitragynine alone | 18.9 (14.0, 24.2) | 40.7 (32.3, 55.8) | Unable to determine due to an adverse reaction (lethality) at 100 mg/kg [up to 7.69% (5.13%) @ 56 mg/kg] | 2.15 (1.33, 3.99) | Not Applicable |
| Mitragynine in the presence of 56 mg/kg ketoconazole | 4.46 (3.57, 5.54) | 33.7 (27.5, 43.3) | Unable to determine due to an adverse reaction (lethality) at 100 mg/kg [up to 18.8% (5.15%) @ 56 mg/kg] | 7.56 (4.96, 12.1) | Not Applicable |
| Rats Trained to Discriminate an Injection of 3.2 mg/kg Morphine from Its Vehicle | |||||
| 7HMG alone | 0.275 (0.0768, 0.411) | 4.73 (3.25, 6.35) | 10.5 (8.89, 12.5) | 17.2 (7.91, 82.7) | 38.2 (21.6, 163) |
| 7HMG in the presence of 56 mg/kg ketoconazole | 0.0285 (0.0224, 0.0346) | 1.84 (1.47, 2.28) | 2.56 (2.17, 3.02) | 64.6 (42.5, 122) | 89.8 (78.0, 135) |
| Mitragynine alone | 29.6 (18.8, 55.9) | 45.7 (36.4, 64.1) | Unable to determine due to an adverse reaction at 100 mg/kg [up to 7.49% (6.46%) @ 5.6 mg/kg] | 1.54 (0.651, 3.41) | Not Applicable |
| Mitragynine in the presence of 56 mg/kg ketoconazole | 6.31 (3.93, 8.69) | 33.0 (27.4, 41.2) | Unable to determine due to an adverse reaction (lethality) at 100 mg/kg [up to 18.1% (5.37%) @ 56 mg/kg] | 5.23 (3.15, 10.5) | Not Applicable |
| Morphine alone | 1.46 (0.941, 1.90) | 19.9 (16.4, 23.7) | 35.8 (32.7, 39.3) | 13.6 (8.63, 25.2) | 24.5 (17.2, 41.8) |
| Morphine alone (females) | 1.70 (0.752, 2.77) | 16.4 (12.6, 20.2) | 37.9 (30.4, 46.8) | 9.65 (4.55, 26.9) | 22.3 (11.0, 62.2) |
| Morphine alone (males) | 1.10 (0.762, 1.42) | 16.0 (10.8, 21.5) | 34.3 (30.7, 38.3) | 14.5 (7.61, 28.2) | 31.2 (21.6, 50.3) |
| Morphine in the presence of 56 mg/kg ketoconazole | 2.35 (1.76, 2.93) | 23.2 (18.8, 28.5) | 33.5 (29.9, 38.1) | 9.87 (6.42, 16.2) | 14.3 (10.2, 21.6) |