Table 2.

IC₅₀ values for [³H]‐S‐CIT displacement and allosteric potency of S‐CIT and the cyano‐containing analogues

Cpd	SERT S1 binding IC 50 (μM)	n	SERT allosteric potency IC 50 (μM)	n	S2: S1 ratio
S‐CIT	0.010 [0.008; 0.013]	3	5.8 [5.4; 6.3]	3	580
2	0.041 [0.032; 0.051]	4	10.1 [10.0; 10.2]	3	250
3	6.4 [4.7; 8.8]	4	3.6 [3.3; 3.8]	3	0.56
4	0.50 [0.42; 0.58]	4	3.6 [3.5; 3.7]	3	7.2
5	0.16 [0.14; 0.18]	4	17 [16; 18]	3	110
6	0.11 [0.09; 0.13]	4	27 [25; 29]	3	250
7	10 [9.2; 12]	4	12 [10; 13]	3	1.1
8	1.4 [1.0; 2.0]	4	8.8 [6.3; 12]	3	6.3

IC₅₀ values were calculated by non‐linear regression analysis either from [³H]‐S‐CIT binding inhibition assays (S1 binding) or from [³H]‐S‐CIT dissociation experiments (S2 binding) in the presence of increasing concentrations of the indicated compound. Data are shown as mean values calculated from means of pIC₅₀ and the SEM interval from pIC₅₀ ± SEM of n independent experiments performed in triplicates for the assessment of S1 binding affinity. See Methods section for the determination and sample size of allosteric potency. Experiments were performed on membrane preparations from COS7 cells transiently expressing SERT.