Interaction between tramadol and two anti-emetics on nociception and gastrointestinal transit in mice

Background: Clinical studies suggest that tramadol-induced analgesia is partially antagonized by ondansetron. Aims: To investigate the type of interaction between tramadol and two anti-emetics on antinociception and gastrointestinal transit in mice. Methods: We assessed the antinociceptive (acetic acid writhing test, plantar test) and antitransit (charcoal meal) effects of tramadol individually, and combined with ondansetron or droperidol in female Swiss CD-1 mice. Isobolograms and analysis of variance were used to determine the type of interaction. Results: In the writhing test, tramadol, ondansetron and droperidol, each induced dose-related inhibition of nociception. The ED50's were: tramadol 4.2 ± 0.33 mg kg-1; ondansetron 1.03 ± 0.05 mg kg-1, and droperidol 1.00 ± 0.14 mg kg-1. Dose-response curves were also obtained with tramadol combined with ondansetron or droperidol at 1:1 fixed ratios. The isobolographic analysis demonstrated antagonism for both combinations. In the plantar test, the ED50 for tramadol was 51.4 ± 2.3 mg kg-1, but no dose-response curves could be obtained with ondansetron or droperidol individually. The interaction was assessed from dose-response curves to tramadol in the presence of a fixed dose of ondansetron (0.1 mg kg-1) or droperidol (0.05 mg kg-1). The results show antagonism between tramadol-ondansetron (p < 0.05) and no interaction for the tramadol-droperidol combination. Both anti-emetics antagonized the antitransit effects of tramadol. Conclusions: The interaction of tramadol with ondansetron or droperidol on antinociception can be antagonistic or additive, depending on the type of stimuli. Both anti-emetics antagonize the anti-transit effects of tramadol. The results demonstrate antagonism between tramadol and the two anti-emetics for analgesia and inhibition of gastrointestinal transit, supporting previous clinical studies. © 2005 European Federation of Chapters of the International Association for the Study of Pain.