Inhibition of serotonin transport by (+)McN5652 is noncompetitive

Abstract Introduction Imaging of the serotonergic innervation of the brain using positron emission tomography (PET) with the serotonin transporter (SERT) ligand [ 11  C] (+)McN5652 might be affected by serotonin in the synaptic cleft if there is relevant interaction between [ 11 C] (+)McN5652 and serotonin at the SERT. The aim of the present study therefore was to pharmacologically characterize the interaction of [ 11 C] (+)McN5652 and serotonin at the SERT. Methods In vitro saturation analyses of [ 3 H]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 [ 11 C] (+)McN5652 PET is not significantly affected by endogenous serotonin.