Table 2.
Combination therapy improves therapeutic window.
| Strain | Drug(s) | ED50 value (±SE; mg/kg, i.p.) | Therapeutic window | |||
|---|---|---|---|---|---|---|
| Motor | Axial | Non-axial | Motor/axial | Motor/non-axial | ||
| SPARC-null | Morphine | 8 (±6.1) | 10 (±4.0) | ~35 (±50) | 0.8 | 0.2 |
| Clonidine | 0.3 (±0.3) | 0.05 (±0.04) | 0.08 (±0.09) | 6.8 | 4.3 | |
| Morphine (+ CLON; 100 : 1) | ~56 (±85) | 0.08 (±0.23) | 3.5 (±6.3) | 700 | 16 | |
|
| ||||||
| WT | Morphine | ~17 (±14) | 18 (±6.0) | 6.0 (±2.0) | 0.9 | 2.8 |
| Clonidine | 0.1 (±0.2) | 8.2 (±21) | 0.1 (±0.2) | 0.01 | 1.0 | |
| Morphine (+ CLON; 100 : 1) | No efficacy | No efficacy | 2.7 (±8.9) | N/A | N/A | |
The Therapeutic window is the ratio of the ED50 value (mg/kg, i.p.) of the undesired effect (motor impairment) to the desired effect (inhibition of axial or non-axial pain). A larger therapeutic window suggests the drug or drug combination will be analgesic at doses that do not produce motor impairment. ~ indicates that the ED50 value was determined by extrapolation if maximum efficacy was less than 50%. NA = not available (the combination lacked efficacy in the rotarod assay in WT mice). Note the much larger therapeutic window achieved with the addition of clonidine to morphine.