Table 4.
Suppression of the histamine induced DMR-Emax after removal of unbound antihistamines.
| 1 h after washout |
2 h after washout |
||||||
|---|---|---|---|---|---|---|---|
| Log [ligand] | Emax, % | Histamine pEC50 | Emax, % | Histamine pEC50 | kreca (min-1) | RecTb (min) | |
| Vehicle control | NA | 100 ± 2 | 6.1 ± 0.1 | 100 ± 2 | 6.2 ± 0.1 | NA | NA |
| Mepyramine | –7.5 | 87 ± 3 | 6.1 ± 0.1 | 96 ± 4 | 6.1 ± 0.1 | 0.027 ± 0.001 | 38 ± 1 |
| Levocetirizine | –7.2 | 19 ± 1 | 5.0 ± 0.1 | 33 ± 2 | 5.4 ± 0.1 | 0.0030 ± 0.0001 | 338 ± 9 |
| Doxepin | –8.3 | 59 ± 6 | 5.8 ± 0.1 | 76 ± 1 | 5.8 ± 0.1 | 0.011 ± 0.001 | 87 ± 6 |
| Olopatadine | –8.1 | 17 ± 2 | 5.3 ± 0.1 | 27 ± 2 | 5.4 ± 0.1 | 0.0024 ± 0.0005 | 429 ± 81 |
| Triprolidine | –7.3 | 72 ± 8 | 5.6 ± 0.2 | 75 ± 6 | 5.6 ± 0.1 | NA | ND |
| Acrivastine | –6.2 | 93 ± 2 | 6.1 ± 0.2 | 101 ± 2 | 6.3 ± 0.1 | 0.038 ± 0.001 | 26 ± 1 |
| Desloratadine | –8.5 | 53 ± 4 | 5.4 ± 0.3 | 63 ± 2 | 5.4 ± 0.1 | 0.0090 ± 0.0007 | 111 ± 8 |
| VUF14454 | –7.2 | 100 ± 3 | 6.1 ± 0.1 | 101 ± 2 | 6.2 ± 0.1 | NA | <30 |
| VUF14544 | –6.6 | 99 ± 3 | 6.1 ± 0.1 | 103 ± 5 | 6.1 ± 0.1 | NA | <30 |
| VUF14506 | –6.7 | 87 ± 2 | 6.1 ± 0.1 | 98 ± 2 | 6.2 ± 0.1 | 0.029 ± 0.003 | 34 ± 3 |
| VUF14493 | –7.4 | 98 ± 3 | 6.2 ± 0.1 | 102 ± 3 | 6.1 ± 0.1 | NA | <30 |
A dose-dependent DMR response was observed for increasing concentrations histamine as was evaluated 1 and 2 h after washing away unbound antihistamines. The EC50 was determined as before (Figure 8) and the Emax value was estimated from the response of 10-4.2 M histamine and normalized to the Emax of vehicle treated cells. Values represent mean and SD of n = 6 measured over two different days.
akrec, observed recovery rate of H1R activity.
bRecT, recovery time (1/krec).