Inhibition of serotonin transport by (+)McN5652 is noncompetitive

Hummerich, René; Schulze, Oliver; Rädler, Thomas; Mikecz, Pal; Reimold, Matthias; Brenner, Winfried; Clausen, Malte; Schloss, Patrick; Buchert, Ralph

doi:10.1016/j.nucmedbio.2005.12.009

« Previous Next »Nuclear Medicine and Biology
Volume 33, Issue 3 , Pages 317-323, April 2006

Inhibition of serotonin transport by (+)McN5652 is noncompetitive

René Hummerich
- Biochemical Laboratory, Central Institute of Mental Health, 68159 Mannheim, Germany
Oliver Schulze
- Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D–20246 Hamburg, Germany
Thomas Rädler
- Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, D-20246 Hamburg, Germany
Pal Mikecz
- Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D–20246 Hamburg, Germany
Matthias Reimold
- Department of Nuclear Medicine, University Hospital Tübingen, D-72076 Tübingen, Germany
Winfried Brenner
- Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D–20246 Hamburg, Germany
Malte Clausen
- Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D–20246 Hamburg, Germany
Patrick Schloss
- Biochemical Laboratory, Central Institute of Mental Health, 68159 Mannheim, Germany
Ralph Buchert
- Department of Nuclear Medicine, University Medical Center Hamburg-Eppendorf, D–20246 Hamburg, Germany
- Corresponding author. Tel.: +49 40 42803 6106; fax: +49 40 42803 5181.

Received 20 September 2005; received in revised form 14 December 2005; accepted 14 December 2005. published online 13 March 2006.

Abstract

Introduction

Imaging of the serotonergic innervation of the brain using positron emission tomography (PET) with the serotonin transporter (SERT) ligand [¹¹C] (+)McN5652 might be affected by serotonin in the synaptic cleft if there is relevant interaction between [¹¹C] (+)McN5652 and serotonin at the SERT. The aim of the present study therefore was to pharmacologically characterize the interaction of [¹¹C] (+)McN5652 and serotonin at the SERT.

Methods

In vitro saturation analyses of [³H]serotonin uptake into HEK293 cells stably expressing the human SERT were performed in the absence and presence of unlabelled (+)McN5652. Data were evaluated assuming Michaelis–Menten kinetics.

Results

Unlabelled (+)McN5652 significantly reduced the maximal rate of serotonin transport V_max of SERT without affecting the Michaelis–Menten constant K_M.

Conclusions

This finding indicates that (+)McN5652 inhibits serotonin transport through the SERT in a noncompetitive manner. This might suggest that [¹¹C] (+)McN5652 PET is not significantly affected by endogenous serotonin.

Keywords: Serotonin, Serotonin transporter, Positron emission tomography, (+)McN5652, Pharmacological profile