Effects of tramadol and O-demethyl-tramadol on human 5-HT reuptake carriers and human 5-HT3A receptors: a possible mechanism for tramadol-induced early emesis.

Martin Barann, Bernd Urban, Ulrike Stamer, Zita Dorner, Heinz Bönisch, Michael Brüss

Klinik und Poliklinik für Anästhesiologie und operative Intensivmedizin, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany. martin.barann@ukb.uni-bonn.de

European journal of pharmacology 2006 Feb 15

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3H]5-HT)-uptake and patch-clamp techniques were used to study the actions of (+) and (-) tramadol and the active metabolites of tramadol, (+) and (-) O-demethyl-tramadol on the human serotonin (5-HT) transporter and the human 5-HT3A receptor, stably expressed in HEK-293 cells. The (+) and (-) enantiomers of tramadol suppressed the human 5-HT transporter concentration-dependently (IC50=1.0 and 0.8 microM, respectively), resulting in 97% and 87% transport inhibition at their respective initial plasma concentrations (9.5 microM). The (+) and (-) enantiomers of the active tramadol metabolite were less potent than tramadol in inhibiting the human 5-HT transporter (IC50=15 and 44 microM, respectively), resulting in 19.2% and 4.8% transport inhibition at their highest plasma concentrations (2.5 microM). In contrast to their potent suppression of the 5-HT transporter, both, (+) and (-) tramadol inhibited 5-HT (30 microM)-induced currents only at substantially higher concentrations (IC50=199 and 251 microM, respectively), resulting in only 6% and 4% inhibition at the initial maximum plasma concentration. A similar low potent inhibition of human 5-HT(3A) receptors was found for (+) and (-) O-demethyl-tramadol (IC50=158 and 63 microM, respectively). In conclusion, at clinical plasma concentrations tramadol potently suppresses the human 5-HT transporter, whereas it has only a slight effect on the human 5-HT3A receptor. The results are compatible with a possible mechanism for tramadol-induced early emesis involving the serotonergic system.

Citation

Martin Barann, Bernd Urban, Ulrike Stamer, Zita Dorner, Heinz Bönisch, Michael Brüss. Effects of tramadol and O-demethyl-tramadol on human 5-HT reuptake carriers and human 5-HT3A receptors: a possible mechanism for tramadol-induced early emesis. European journal of pharmacology. 2006 Feb 15;531(1-3):54-8