3.1.2. Monoamine uptake inhibition in transfected HEK293 cells
The corresponding IC50 values and hDAT/hSERT inhibition ratios are presented in Table 1 and concentration-response curves are depicted in Figure S2. While assessing uptake-1 assays, all tested drugs displayed low IC50 values for hDAT and negligible activity at hSERT. Additionally, the order of potencies for hDAT was as follows: α-PVP≈N-ethylpentedrone≈α-PpVP>pentedrone>N,N-diethyl-pentedrone ;F(4,10)=30.61). The order of potency for hSERT was as follows: pentedrone≈N-ethyl-pentedrone>>α-PVP>N,N-diethyl-pentedrone≈α-PpVP; F(4,10)=179.1). It is important to point out the very low inhibitory potencies of N,N-diethyl-pentedrone, α-PVP and α-PpVP when studying [3H]5-HT uptake inhibition at hSERT. However, an estimation of the IC50 values, as well as hDAT/hSERT ratios, were calculated in order to perform the corresponding correlation analysis. Accordingly, all compounds appeared to be >100-fold more potent blocking capacity at hDAT over hSERT.
Molecular and physicochemical descriptors were also calculated for the different amino-substituents, correlating them with some QSAR parameters such as CLogP, total surface area, volume and CMR. As shown in Table 2, hSERT, but not hDAT IC50 values, significantly correlated with CLogP, total surface area, volume and CMR of the amino-substituents. In addition, the hDAT/hSERT ratios also correlated with CLogP.
With regards to uptake-2 inhibition experiments (Table 1; Figure S2), α-aminovalerophenone derivatives blocked hOCT-2 within the IC50value range of 10–60 µM, with no considerable effect on hOCT-3.