Isobolographic analyses of the gabapentin-metamizol combination after local peripheral, intrathecal and oral administration in the rat

This study was designed to evaluate the possible antinociceptive interaction between gabapentin and metamizol on formalin-induced nociception. Gabapentin, metamizol or a fixed dose-ratio combination of both drugs were assessed after local peripheral, intrathecal and oral administration in rats. Isobolographic analyses were employed to define the nature of the interaction between drugs. Gabapentin, metamizol and gabapentin-metamizol combinations yielded a dose-dependent antinociceptive effect when administered by the three different routes. ED₃₀ values were estimated for the individual drugs and isobolograms were constructed. Theoretical ED₃₀ values for the combination estimated from the isobolograms were 21.11 ± 1.17 μg/paw, 104.6 ± 5.5 μg/rat and 78.8 ± 5.5 mg/kg for the local peripheral, intrathecal and oral administration routes, respectively. These values were significantly higher than the experimentally obtained ED ₃₀ values which were 11.3 ± 1.5 μg/paw, 36.8 ± 3.1 μg/rat and 15 ± 1.2 mg/kg indicating a synergistic interaction. Systemic administration resulted in the highest synergism. Data confirm that low doses of the gabapentin and metamizol can interact synergistically to reduce formalin-induced nociceptive behavior suggesting that this combination could be useful to treat inflammatory pain in humans.