{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,29]],"date-time":"2025-10-29T03:17:24Z","timestamp":1761707844380},"reference-count":34,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2012,1,11]],"date-time":"2012-01-11T00:00:00Z","timestamp":1326240000000},"content-version":"vor","delay-in-days":1928,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European Journal of Pain"],"published-print":{"date-parts":[[2006,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:italic>Background<\/jats:italic> Clinical studies suggest that tramadol\u2010induced analgesia is partially antagonized by ondansetron.<\/jats:p><jats:p><jats:italic>Aims<\/jats:italic> To investigate the type of interaction between tramadol and two anti\u2010emetics on antinociception and gastrointestinal transit in mice.<\/jats:p><jats:p><jats:italic>Methods<\/jats:italic> 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\u20101 mice. Isobolograms and analysis of variance were used to determine the type of interaction.<\/jats:p><jats:p><jats:italic>Results<\/jats:italic> In the writhing test, tramadol, ondansetron and droperidol, each induced dose\u2010related inhibition of nociception. The ED<jats:sub>50<\/jats:sub>'s were: tramadol 4.2 \u00b1 0.33 mg kg<jats:sup>\u22121<\/jats:sup>; ondansetron 1.03 \u00b1 0.05 mg kg<jats:sup>\u22121<\/jats:sup>, and droperidol 1.00 \u00b1 0.14 mg kg<jats:sup>\u22121<\/jats:sup>. Dose\u2010response curves were also obtained with tramadol combined with ondansetron or droperidol at 1:1 fixed ratios. The isobolographic analysis demonstrated antagonism for both combinations.<\/jats:p><jats:p>In the plantar test, the ED<jats:sub>50<\/jats:sub> for tramadol was 51.4 \u00b1 2.3 mg kg<jats:sup>\u22121<\/jats:sup>, but no dose\u2010response curves could be obtained with ondansetron or droperidol individually. The interaction was assessed from dose\u2010response curves to tramadol in the presence of a fixed dose of ondansetron (0.1 mg kg<jats:sup>\u22121<\/jats:sup>) or droperidol (0.05 mg kg<jats:sup>\u22121<\/jats:sup>). The results show antagonism between tramadol\u2014ondansetron (<jats:italic>p<\/jats:italic> &lt; 0.05) and no interaction for the tramadol\u2014droperidol combination. Both anti\u2010emetics antagonized the antitransit effects of tramadol.<\/jats:p><jats:p><jats:italic>Conclusions<\/jats:italic> The interaction of tramadol with ondansetron or droperidol on antinociception can be antagonistic or additive, depending on the type of stimuli. Both anti\u2010emetics antagonize the anti\u2010transit effects of tramadol. The results demonstrate antagonism between tramadol and the two anti\u2010emetics for analgesia and inhibition of gastrointestinal transit, supporting previous clinical studies.<\/jats:p>","DOI":"10.1016\/j.ejpain.2005.10.002","type":"journal-article","created":{"date-parts":[[2005,11,22]],"date-time":"2005-11-22T12:31:26Z","timestamp":1132662686000},"page":"629-629","source":"Crossref","is-referenced-by-count":21,"title":["Interaction between tramadol and two anti\u2010emetics on nociception and gastrointestinal transit in 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