Activities derived from the receptor screen at various sites expressed as % displacement at 10 μM and estimated Ki values relative to DAT affinity
Sites at which at least one of the compounds showed greater than 50% inhibition of radioligand binding at 10 μM are shown.
| Target | % Inhibition | Relative to DATa | ||
|---|---|---|---|---|
| LX19 (β) | LX20 (α) | LX19 (β) | LX20 (α) | |
| Adenosine A2A | 57 | Inactive | 60 | Inactive |
| Adrenergic α2A | 94 | 99 | <7.3 | <0.56 |
| DA D1R | 76 | 80 | 22 | 1.8 |
| DA D2LR | Inactive | 63 | Inactive | 2.6 |
| DA D3R | 60 | 97 | 32 | <0.56 |
| Histamine H2 | Inactive | 69 | Inactive | 0.16 |
| Muscarinic M2 | 85 | 99 | 10 | <0.53 |
| Opioid δ | 58 | 76 | 36 | 1.5 |
| Opioid κ | 84 | 77 | 12 | 1.6 |
| Opioid μ | Inactive | 52 | Inactive | 5.3 |
| 5-HT1A | 65 | 102 | 42 | <0.74 |
| 5-HT2A | 96 | 98 | <5.1 | <0.45 |
| Na Channel, Site 2 | 94 | 98 | <17 | <1.4 |
↵a See Materials and Methods for details regarding derivation of affinities relative to DAT. Briefly, for sites at which compounds produced between 10 and 90% displacement, an IC50 value was derived by linear interpolation assuming a displacement curve spanning a 100-fold domain of concentrations. For sites at which the displacement was >90%, IC50 values were estimated to be <1 μM. The compound was considered inactive at sites for which the displacement by 10 μM was <10%. Ki values were derived from estimated IC50 values and the Cheng-Prusoff equation using Kd values of radioligands provided by the vendor. This method follows a practice used by Kosterlitz et al. (1973) to estimate potencies of opioids for inhibition of guinea pig ileum contractions at single concentrations. The Ki values are presented in the table as ratio Ki values (LX compound/DAT), with values for the DAT determined in the present study (Table 3).