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.