Table 1.
In vitro binding and functional activity at human recombinant OX1 and OX2 receptors.
| Compound | Receptor binding affinity, Ki(nM)a | Functional antagonist activity, Kb (nM)b | ||||
|---|---|---|---|---|---|---|
| OX1 | OX2 | hOX1 | hOX2 | rOX1 | rOX2 | |
| LSN2424100 | 393 ± 47 (3) | 4.49 ± 1.39 (3) | 90.3 ± 17.7 (2) | 0.44 ± 0.11 (3) | 175 ± 41 (2) | 0.83 ± 0.19 (2) |
| SB334867 | 173 ± 11 (3) | >10,000 (3) | 8.68 ± 1.76 (3) | >10,000 (3) | 7.1 ± 0.71 (3) | >10,000 (3) |
| Almorexant (S) | 21 ± 3.2 (2) | 6.9 ± 0.18 (2) | 2.32 ± 0.18 (3) | 1.73 ± 0.35 (3) | 3.2 ± 0.7 (4) | 4.4 ± 1.6 (4) |
| Almorexant (R) | >10,000 (2) | >10,000 (2) | >10,000 (2) | >10,000 (2) | NT | NT |
Radioligand binding was performed using HEK293 membranes expressing either human OX1 or OX2 receptors in the presence of [125I]-orexin A with a 90 min incubation time. Data represent the mean ± s.e.m. performed on separate occasions with the number of independent experiments in parenthesis. (R) is the inactive enantiomer of almorexant.
Inhibition of calcium mobilization from HEK293 cells stably expressing human or rat OX1 or OX2 receptors, respectively. Functional antagonist activity was determined by measuring the effects of an EC70 concentration of orexin-A. Data represent the mean ± s.e.m. performed on separate occasions with the number of independent experiments in parenthesis. NT = not tested.