Fulltext

Effects of opioids on human serotonin transporters

Barann, M. ; Stamer, U. ; Lyutenska, M. ; Stüber, F. ; Bönisch, H. ; Urban, B.

In: Naunyn-Schmiedeberg's Archives of Pharmacology, 2015, vol. 388, no. 1, p. 43-49

Aggiungi alla tua lista
    Titre
    • Effects of opioids on human serotonin transporters
    Auteur
    • Barann, M.. Department of Anaesthesiology and Intensive Care Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
    • Stamer, U.. Department of Anaesthesiology and Pain Medicine, Inselspital and Department of Clinical Research, University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
    • Lyutenska, M.. Department of Anaesthesiology and Intensive Care Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
    • Stüber, F.. Department of Anaesthesiology and Pain Medicine, Inselspital and Department of Clinical Research, University of Bern, Freiburgstrasse, 3010, Bern, Switzerland
    • Bönisch, H.. Institute for Pharmacology and Toxicology, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
    • Urban, B.. Department of Anaesthesiology and Intensive Care Medicine, University of Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany
    Type de document
    • Postprint
    Langue
    • Inglese
    Publié dans
    • Naunyn-Schmiedeberg's Archives of Pharmacology, 2015, vol. 388, no. 1, p. 43-49. Springer Berlin Heidelberg
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:331960
    Summary
    The serotonin (5-hydroxtryptamine, 5-HT) system plays a role in analgesia and emesis. The aim of this study was to test whether opioids or ketamine inhibit the human 5-HT transporter and whether this increases free plasma 5-HT concentrations. HEK293 cells, stably transfected with the human 5-HT transporter cDNA, were incubated with morphine, hydromorphone, fentanyl, alfentanil, pethidine (meperidine), tramadol, ketamine, and the reference substance citalopram (specific 5-HT transporter inhibitor). The uptake of [3H]5-HT was measured by liquid scintillation counting. In a second series of experiments, study drugs were incubated with plasma of ten healthy blood donors and change of 5-HT plasma-concentrations were measured (ELISA). The end point was the inhibition of the 5-HT transporter by different analgesics either in HEK293 cells or in human platelets ex vivo. Tramadol, pethidine, and ketamine suppressed [3H]5-HT uptake dose-dependently with an IC50 of 1, 20.9, and 230μM, respectively. These drugs also prevented 5-HT uptake in platelets with an increase in free plasma 5-HT. Free 5-HT concentrations in human plasma were increased by citalopram 1μM, tramadol 20μM, pethidine 30μM, and ketamine 100μM to 280 [248/312]%, 269 [188/349]%, and 149 [122/174]%, respectively, compared to controls without any co-incubation (means [95% CI]; all p < 0.005). No change in both experimental settings was observed for the other opioids. Tramadol and pethidine inhibited the 5-HT transporter in HEK293 cells and platelets. This inhibition may contribute to serotonergic effects when these opioids are given in combination, e.g., with monoamine oxidase inhibitors or selective serotonin reuptake inhibitors.