The synergistic interaction between rilmenidine and paracetamol in the writhing test in mice

The aim of the study was to ascertain antinociceptive effects of rilmenidine, a second-generation imidazoline-alpha-2-adrenoreceptor agonist, and to see whether rilmenidine was able to increase the analgesic effects of paracetamol in the writhing test in mice. An acetic acid (0.7%) solution was injected into the peritoneal cavity and the number of writhes was counted. The influence on locomotor performance was tested using the rotarod test. Rilmenidine, paracetamol, and rilmenidine–paracetamol fixed-ratio combinations produced dose-dependent antinociceptive effects. ED₅₀ values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical additive ED₅₀ value for the rilmenidine–paracetamol combination was 109.23 ± 35.05 mg/kg. This value was significantly greater than the observed ED₅₀ value which was 56.35 ± 20.86 mg/kg, indicating a synergistic interaction. Rilmenidine did not impair motor coordination, as measured by the rotarod test, at antinociceptive and higher doses.