The synergistic interaction between rilmenidine and paracetamol in the writhing test in mice |
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Authors: | M. Soukupová T. Doležal M. Kršiak |
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Affiliation: | (1) Department of Pharmacology, Third Faculty of Medicine, Charles University of Prague, Ruska 87, 100 34 Prague, Czech Republic |
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Abstract: | 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. |
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Keywords: | Rilmenidine Paracetamol Antinociception Pain Imidazoline Receptors Alpha-2-adrenoceptors |
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