The tramadol metabolite O-desmethyl tramadol inhibits substance P-receptor functions expressed in Xenopus oocytes

Tramadol has been widely used as analgesic. o-desmethyl tramadol (odt) is one of the main metabolites of tramadol,having much greater analgesic potency than tramadol itself. substance p receptors (spr) are well known to modulate nociceptive transmission within the spinal cord. in this study,we investigated the effects of odt on spr expressed in xenopus oocytes by examining sp-induced ca2+-activated cl- currents. odt inhibited the spr-induced cl- currents at pharmacologically relevant concentrations. the protein kinase c (pkc) inhibitor bisindolylmaleimide i did not abolish the inhibitory effects of odt on sp-induced ca2+-activated cl- currents. the results suggest that the tramadol metabolite odt inhibits the spr functions,which may be independent of activation of pkc-mediated pathways. © the japanese pharmacological society.