Potencies of various selective OX1, OX2, and dual OX1/OX2 antagonists on inhibition of orexin-A (EC80)-induced intracellular Ca2+ mobilization
IC50, Kb, and nH values for the inhibition of orexin-A (EC80)-evoked [Ca2+]i response by various antagonists in the CHO(dHFr−)-hOX1 and hOX2 stable cell lines were calculated as described under Materials and Methods. Values are mean ± S.E. calculated from three independent experiments (each performed in duplicate).
| OX Antagonists | hOX1 | hOX2 | ||||
|---|---|---|---|---|---|---|
| IC50 | Kb | nH | IC50 | Kb | nH | |
| nM | nM | |||||
| Almorexant | 24.1 ± 5.2 | 3.3 ± 0.4 | 1.5 ± 0.5 | 15.6 ± 5.2 | 1.5 ± 0.2 | 1.9 ± 0.4 |
| Cp-1 | 78.6 ± 6.7 | 10.8 ± 0.9 | 0.9 ± 0.1 | 4.8 ± 1.0 | 0.5 ± 0.1 | 1.8 ± 0.1 |
| Cp-2 | 11.1 ± 2.4 | 2.7 ± 0.2 | 1.3 ± 0.2 | 19.3 ± 0.5 | 1.7 ± 0.1 | 1.1 ± 0.0 |
| Cp-3 | 51.4 ± 4.0 | 4.7 ± 0.8 | 1.2 ± 0.1 | 37.6 ± 6.1 | 3.7 ± 0.7 | 1.0 ± 0.0 |
| SB-674042 | 2.2 ± 0.2 | 0.5 ± 0.0 | 2.0 ± 0.4 | 531.0 ± 36.7 | 137.7 ± 9.5 | 0.9 ± 0.0 |
| SB-408124 | 50.7 ± 3.2 | 12.4 ± 0.8 | 3.5 ± 0.8 | 4000.0 ± 2000.0 | 1037.0 ± 519.0 | 7.0 ± 3.0 |
| SB-334867 | 31.3 ± 4.0 | 7.7 ± 1.2 | 3.3 ± 0.5 | 1870.0 ± 102.0 | 484.8 ± 26.5 | 3.9 ± 0.0 |
| EMPA | >10,000 | 8.8 ± 1.7 | 0.8 ± 0.2 | 0.9 ± 0.0 | ||
| Cp-4 | 2070.0 ± 150.0 | 507.3 ± 52.5 | 1.9 ± 0.5 | 15.6 ± 2.2 | 1.5 ± 0.2 | 1.3 ± 0.1 |
| Cp-5 | >10,000 | 198.0 ± 73.3 | 20.3 ± 7.1 | 0.8 ± 0.0 | ||