TABLE 3.
Emax and ED50 values of fixed-proportion agonist/antagonist mixtures in the warm water tail-withdrawal assay of thermal antinociception in mice
Emax, ED50, and Hill coefficient values are derived from the dose-response curves shown in Fig. 4. Fixed-proportion dose ratios are expressed as X:1 agonist/antagonist, which are fentanyl/naltrexone (F/N) and CP55,940/rimonabant (C/R). Emax values are expressed as %MPE. ED50 values are expressed as agonist dose in micrograms per kilogram. For mixtures, the antagonist concentration at the ED50 value can be calculated as ED50 ÷ fixed-proportion dose ratio of agonist to antagonist. All values are means (95% confidence limits) (n = 8–10). Values without any overlap in confidence limits are P < 0.05 different from each other, although upper or both confidence limits of some values could not be accurately determined.
| Receptor | Mixture | Emax (%MPE) | ED50 | Hill Coefficient |
|---|---|---|---|---|
| µg/kg | ||||
| MOR | Fentanyl | 100 | 20.2 (15.2–23.7) | 2.90 (2.03–4.67) |
| MOR | 35.8 F:1 N | 100 | 35.6 (31.2–43.5) | 4.06 (1.97–∞) |
| MOR | 11.9 F:1 N | 80.3 (61.8–98.8) | 60.7 (43.7–83.3) | 2.40 (1.37–∞) |
| MOR | 6.89 F:1 N | 45.5 (28.2–62.8) | 35.8 (22.1–56.2) | 2.45 (1.03–∞) |
| MOR | 3.97 F:1 N | 26.1 (7.31–44.8) | 42.2 (21.8–∞) | 5.67 (0.54–∞) |
| MOR | 1.32 F:1 N | −2.09 (−5.08 to 0.89) | N.D. | N.D. |
| MOR | Naltrexone | 0.42 (−2.08 to 2.91) | N.D. | N.D. |
| CB1R | CP55,940 | 100 | 665 (518–845) | 1.73 (1.22–2.58) |
| CB1R | 5.56 C:1 R | 86.2 (65.6–106.8) | 259 (174–395) | 2.35 (1.08–∞) |
| CB1R | 1.89 C:1 R | 82.0 (58.3–105.7) | 997 (589–1556) | 2.09 (0.97–∞) |
| CB1R | 0.625 C:1 R | 65.2 (37.8–92.6) | 614 (317–1137) | 1.34 (0.67–3.17) |
| CB1R | 0.213 C:1 R | 16.6 (−0.68 to 33.9) | 612 (N.D.) | 2.22 (−0.03 to ∞) |
| CB1R | Rimonabant | 5.9 (−15.9 to 23.8) | N.D. | N.D. |
N.D., values could not be determined.