Morphine and Fentanyl Hypnotic Interactions with Thiopental

The effects of morphine thiopental and fentanyl-thiopental combinations on the righting reflex were studied in rats. Doses that block the righting reflex for the agents given alone and for their combinations were determined with a probit procedure and compared with an isobolographic analysis. Interaction between morphine or fentanyl and thiopental on blockade of the righting reflex were both found to be synergistic. The degree of synergism was relatively small for the fentanyl-thiopental combination; the maximal deviation from additive interaction (expected/observed ratio) for ED₅₀ dose level was 1.15 (P < 0.01). The degree of synergism was greater for the morphine-thiopental combination; the maximal deviation from additive interaction was 2.27 (P < 0.001). Comparison of the results with the outcomes of opioid-barbiturate interactions in relation to blockade of purposeful movement response to tail clamping, which was antagonistic, shows that the combination of a barbiturate with an opioid gives different outcomes for different end-points of anesthesia. This suggests that the anesthetic effect of an agent is composed of several components, each with a different mechanism of action.