Synergistic antinociceptive interactions between fospropofol and alfentanil in mice

Combination therapy, which provides the opportunity to achieve optimal analgesia with reduced side effects at lower drug doses, is a valid approach for the treatment of pain. The analgesic interaction between fospropofol and alfentanil has not been investigated till date. We sought to determine the nature of the interaction between fospropofol and alfentanil in mice models of the formalin test, hot-plate test and the tail-flick test.

The effects of fospropofol, alfentanil and their combinations were examined in the formalin-induced paw inflammatory hyperalgesia, the hot-plate test and the tail-flick test in mice. In the three models, dose-response curves were established and their respective ED50 (50% effective dose) values were determined separately for each agent. Fixed-ratio combinations of fospropofol and alfentanil were tested for their combined antinociceptive effects, and the type of interaction was determined by the isobolographic analysis.

Fospropofol, alfentanil and their combination produced a dose-dependent decrease in the number of flinches during phase 1 of the formalin test. In the hot-plate test and in the tail-flick test, fospropofol, alfentanil and their combination significantly and dose dependently prolonged the latency of withdrawal. In the three models, isobolographic analysis revealed a significant synergistic interaction between fospropofol and alfentanil. The ED50 value for the drug combination was significantly lower than the theoretical additive value (p<0.05).

The results demonstrate that fospropofol and alfentanil provide synergistic antinociceptive interactions in the formalin, hot-plate, and tail-flick tests. The observed synergistic interaction between fospropofol and alfentanil are indicative of the effectiveness of the combination treatment in pain management and should be explored further in patients undergoing minor surgical procedures.