Synergistic interaction of gabapentin with tiagabine in the formalin test in mice: An isobolographic analysis

ABSTRACTThe aim of this study was to determine the analgesic effect of gabapentin and tiagabine – two antiepileptic drugs, administered alone and in combination at the fixed‐ratio of 1:1, in two phases of the formalin test in mice. Log‐probit analysis was used to evaluate dose–response effects and calculate the ED50values for gabapentin, tiagabine, and their combination at the fixed‐ratio of 1:1 in the phases I and II of the formalin test in mice. The types of interactions between both antiepileptic drugs were characterized using the isobolographic analysis.Results indicated that gabapentin and tiagabine produced the antinociceptive effect in both phases of the formalin test. The ED50values for gabapentin and tiagabine, administered singly, in the phase I of the formalin test were 29.59 and 2mg/kg, whereas in the phase II of the formalin test were 8.22 and 0.50mg/kg, respectively. With isobolography, the ED50mixvalues at the fixed‐ratio combination of 1:1 were 7.30mg/kg (phase I) and 0.48mg/kg (phase II), indicating both additive and supra‐additive (synergistic) interactions between gabapentin and tiagabine in the formalin test in mice.In conclusion, the combination of gabapentin with tiagabine at the fixed‐ratio of 1:1 exerted additive interaction in the phase I and synergistic interaction in the phase II of the formalin test in mice. If the results from this study could be extrapolated to clinical settings, the combination of tiagabine with gabapentin might be beneficial in the pain relief in humans.