3.2. Transporter binding affinities
The binding affinities of the α-aminovalerophenone derivatives for hDAT
and hSERT were assessed by their ability to displace the corresponding
radioligand binding to membranes prepared from HEK293 cells expressing
these transporters. Their affinity constants (Ki) are summarized
in Table 1. All drugs exhibited higher binding affinity for hDAT in the
medium-low nanomolar range (< 400 nM), when compared to hSERT
(> 10000 nM). Therefore, all the compounds seem to be
hDAT-selective. For instance, N-ethyl-pentedrone, α-PVP and α-PpVP were
more potent than cocaine in binding to hDAT. Conversely, all drugs
presented substantially lower affinity to hSERT, with pentedrone showing
the highest affinity (Ki ). α-PVP and the compound with the
bulkier amino-substituent (α-PpVP) displayed poor binding affinity to
hSERT. These results are in accordance with uptake-1 experiments in
which we demonstrated a progressively lower potency at hSERT when
increasing the volume, sterik bulk or total surface area of the
amino-substituent.