Clinical studies suggest that tramadol-induced analgesia is partially antagonized by ondansetron.

To investigate the type of interaction between tramadol and two anti-emetics on antinociception and gastrointestinal transit in mice.

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.

In the writhing test, tramadol, ondansetron and droperidol, each induced dose-related inhibition of nociception. The ED₅₀’s were: tramadol 4.2±0.33mgkg⁻¹; ondansetron 1.03±0.05mgkg⁻¹, and droperidol 1.00±0.14mgkg⁻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±2.3mgkg⁻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 (0.1mgkg⁻¹) or droperidol (0.05mgkg⁻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.

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.