Effects of Opioids on Human Serotonin Transporters

Overview

Journal Naunyn Schmiedebergs Arch Pharmacol

Specialty Pharmacology

Date 2014 Oct 22

PMID 25332055

Citations 14

Authors

M Barann

U M Stamer

M Lyutenska

F Stuber

H Bonisch

B Urban

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Prenatal Opioid and Alcohol Exposures: Association with Altered Placental Serotonin Transporter Structure and/or Expression.

Darbinian N, Merabova N, Tatevosian G, Adele S, Darbinyan A, Morrison M Int J Mol Sci. 2024; 25(21).

PMID: 39519122 PMC: 11546934. DOI: 10.3390/ijms252111570.

Microdosing ketamine in Drosophila does not block serotonin reuptake, but causes complex behavioral changes mediated by glutamate and serotonin receptors.

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Microdosing ketamine in does not inhibit SERT like SSRIs, but causes behavioral changes mediated by glutamate and serotonin receptors.

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Interactions of fentanyl with blood platelets and plasma proteins: platelet sensitivity to prasugrel metabolite is not affected by fentanyl under in vitro conditions.

Bednarek R, Luzak B, Golanski J, Boncler M Pharmacol Rep. 2023; 75(2):423-441.

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Characterization of the Presence and Function of Platelet Opioid Receptors.

Gruba S, Francis D, Meyer A, Spanolios E, He J, Meyer B ACS Meas Sci Au. 2022; 2(1):4-13.

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