Synergistic interaction between rilmenidine and ibuprofen in the writhing test in mice.
OBJECTIVE
The aim of the study was to ascertain whether rilmenidine, a second generation imidazoline-alpha-2-adrenoreceptor agonist, is able to increase analgesic effects of ibuprofen in the writhing test in mice. Experimental studies combining these agents have not yet been published.


METHODS
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.


RESULTS
Rilmenidine, ibuprofen, and rilmenidine-ibuprofen 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-ibuprofen combination was 34.00 +/- 9.39 mg/kg. This value was significantly greater than the observed ED50 value which was 18.07 +/- 5.41 mg/kg, indicating a synergistic interaction. Rilmenidine did not impair motor coordination, as measured by the rotarod test, at antinociceptive and higher doses.


CONCLUSIONS
The present results suggest that rilmenidine enhances the analgesic activity of ibuprofen. If rilmenidine produces antinociception in humans, then the synergistic antinociception of rilmenidine with ibuprofen could offer therapeutic advantage for clinical treatment of pain.
Soukupova
Marie
M
Department of Pharmacology, Charles University in Prague, Czech Republic. marie.soukupova@lf3.cuni.cz
Dolezal
Tomas
T
Krsiak
Miloslav
M
D019342:Acetic Acid; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007052:Ibuprofen / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D010080:Oxazoles / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D010147:Pain Measurement; D000077769:Rilmenidine; D045442:Rotarod Performance Test
D000316:Adrenergic alpha-Agonists; D018712:Analgesics, Non-Narcotic; D010080:Oxazoles; D000077769:Rilmenidine; D019342:Acetic Acid; D007052:Ibuprofen