Effects of opioids on human serotonin transporters.

Barann, M; Stamer, Ulrike; Lyutenska, M; Stüber, Frank; Bönisch, H; Urban, B (2015). Effects of opioids on human serotonin transporters. Naunyn-Schmiedeberg's archives of pharmacology, 388(1), pp. 43-49. Springer 10.1007/s00210-014-1056-3

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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 [(3)H]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 [(3)H]5-HT uptake dose-dependently with an IC50 of 1, 20.9, and 230 μM, 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 1 μM, tramadol 20 μM, pethidine 30 μM, and ketamine 100 μM 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Intensive Care, Emergency Medicine and Anaesthesiology (DINA) > Clinic and Policlinic for Anaesthesiology and Pain Therapy

UniBE Contributor:

Stamer, Ulrike and Stüber, Frank

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0028-1298

Publisher:

Springer

Language:

English

Submitter:

Jeannie Wurz

Date Deposited:

23 Jun 2015 08:54

Last Modified:

23 Jan 2018 12:15

Publisher DOI:

10.1007/s00210-014-1056-3

PubMed ID:

25332055

BORIS DOI:

10.7892/boris.69697

URI:

https://boris.unibe.ch/id/eprint/69697

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