Synergism between COX-3 inhibitors in two animal models of pain.
OBJECTIVE
The antinociception induced by the intraperitoneal coadministration in mice of combinations of metamizol and paracetamol was evaluated in the tail flick test and orofacial formalin test.


METHODS
The antinociception of each drugs alone and the interaction of the combinations was evaluated by isobolographic analysis in the tail-flick and in the formalin orofacial assay of mice.


RESULTS
Mice pretreated with the drugs demonstrated that the antinociception of metamizol and paracetamol is dose-dependent. The potency range on the antinocifensive responses for metamizol or paracetamol was as follows: orofacial (Phase II) > orofacial (Phase I) > tail flick. In addition, the coadministration of metamizol with paracetamol induced a strong synergistic antinociception in the algesiometer assays. Both drugs showed effectiveness in inflammatory pain.


CONCLUSIONS
These actions can be related to the differential selectivity of the drugs for inhibition of COX isoforms and also to the several additional antinociception mechanisms and pathways initiated by the analgesic drugs on pain transmission. Since the efficacy of the combination of metamizol with paracetamol has been demonstrated in the present study, this association could have a potential beneficial effect on the pharmacological treatment of clinical pain.
Muñoz
J
J
Pharmacology Program, Faculty of Medicine, ICBM, Universidad de Chile, Clasificador 70.000, Independencia 1027, Santiago, 7, Chile.
Navarro
C
C
Noriega
V
V
Pinardi
G
G
Sierralta
F
F
Prieto
J C
JC
Miranda
H F
HF
D000082:Acetaminophen / Q000627:therapeutic use; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D004177:Dipyrone / Q000627:therapeutic use; D004195:Disease Models, Animal; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005557:Formaldehyde / Q000494:pharmacology; D006358:Hot Temperature; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D010147:Pain Measurement / Q000379:methods; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*
D016861:Cyclooxygenase Inhibitors; D005557:Formaldehyde; D000082:Acetaminophen; D004177:Dipyrone; D011451:Prostaglandin-Endoperoxide Synthases; C466421:cyclooxygenase-3