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. ED(50) values were estimated for the individual drugs and an isobologram was constructed. The derived theoretical additive ED(50) value for the rilmenidine-paracetamol combination was 109.23 +/- 35.05 mg/kg. This value was significantly greater than the observed ED(50) 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.
Soukupová
M
M
Department of Pharmacology, Third Faculty of Medicine, Charles University of Prague, Ruska 87, 100 34, Prague, Czech Republic. Marie.Soukupova@lf3.cuni.cz
Dolezal
T
T
Krsiak
M
M
D000082:Acetaminophen / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D008297:Male; D051379:Mice; D010080:Oxazoles / Q000008:administration & dosage*; D010146:Pain / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D000077769:Rilmenidine; D045442:Rotarod Performance Test / Q000379:methods
D010080:Oxazoles; D000082:Acetaminophen; D000077769:Rilmenidine