Inhibition of serotonin transport by (+)McN5652 is noncompetitive.
BACKGROUND
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.
Hummerich
René
R
Biochemical Laboratory, Central Institute of Mental Health, 68159 Mannheim, Germany.
Schulze
Oliver
O
Rädler
Thomas
T
Mikecz
Pal
P
Reimold
Matthias
M
Brenner
Winfried
W
Clausen
Malte
M
Schloss
Patrick
P
Buchert
Ralph
R
D001667:Binding, Competitive; D002478:Cells, Cultured; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology*; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*
D007546:Isoquinolines; D012702:Serotonin Antagonists; D012701:Serotonin; C058079:McN 5652