Spinal antinociceptive synergy between clonidine and morphine, U69593, and DPDPE: Isobolographic analysis

Abstract

The spinal antinociceptive interaction between the opiate receptor subtype agonists morphine (μ), U69593 (K) and [D-Pen^2,5]-enkephalin (DPDPE; σ) with clonidine (α₂ adrenergic) was examined. Male SD rats received fixed ratios of clonidine to morphine (10:1), U69593 (1:3), or DPDPE (10:1) through catheters terminating at the lumbar cord. Graded dose-response curves (DRC) were constructed from tail-flick latencies converted to % maximal possible effect (%MPE), and the ED₅₀ calculated. The DRCs of morphine and U69593 but not of DPDPE were parallel to the DRC of the opiate plus clonidine. Synergy was determined by isobolographic analysis. The ED₅₀ values for the mixtures were significantly less than the theoretical additive ED₅₀ values, indicating synergy between clonidine and morphine, U69593, or DPDPE.