The pK i and pIC50 values of the tested inverse agonists for the human H1 receptor and their intrinsic activities (α)
| Compound | pKi | n | [3H]InsP3Assay | NF-κB Reporter-Gene Assay | ||||||
|---|---|---|---|---|---|---|---|---|---|---|
| pIC50 | % | α | n | pIC50 | % | α | n | |||
| Acrivastine | 7.5 ± 0.1 | 3 | 7.6 ± 0.1 | −51 ± 10 | −1.00 | 3 | 7.4 ± 0.1 | −58 ± 5 | −0.72 ± 0.06 | 6 |
| (R)-Cetirizine | 7.8 ± 0.1 | 3 | 7.4 ± 0.1 | −49 ± 4 | −0.96 ± 0.08 | 4 | 8.2 ± 0.1 | −59 ± 3 | −0.73 ± 0.04 | 13 |
| (S)-Cetirizine | 6.8 ± 0.1 | 3 | 6.6 ± 0.2 | −46 ± 3 | −0.90 ± 0.06 | 4 | 6.6 ± 0.1 | −62 ± 3 | −0.77 ± 0.04 | 13 |
| Diphenhydramine | 7.9 ± 0.1 | 3 | N.D. | 7.2 ± 0.2 | −64 ± 9 | −0.79 ± 0.11 | 4 | |||
| 4-Methyldiphenhydramine | 8.8 ± 0.1 | 5 | N.D. | 8.1 ± 0.1 | −61 ± 5 | −0.76 ± 0.06 | 4 | |||
| 4,4-Dimethyldiphenhydramine | 7.4 ± 0.1 | 3 | N.D. | 7.6 ± 0.1 | −67 ± 5 | −0.83 ± 0.06 | 5 | |||
| Doxepine | 10.0 ± 0.1 | 6 | N.D. | 9.4 ± 0.3 | −74 ± 4 | −0.92 ± 0.05 | 9 | |||
| Ebastine | 8.0 ± 0.1 | 5 | N.D. | 7.4 ± 0.2 | −63 ± 4 | −0.78 ± 0.05 | 3 | |||
| Epinastine | 8.9 ± 0.1 | 3 | 8.7 ± 0.2 | −49 ± 8 | −0.96 ± 0.16 | 4 | 8.1 ± 0.2 | −70 ± 3 | −0.87 ± 0.04 | 4 |
| KW 4679 | 8.0 ± 0.1 | 3 | N.D. | 9.0 ± 0.1 | −61 ± 6 | −0.76 ± 0.07 | 4 | |||
| Loratadine | 6.8 ± 0.1 | 6 | 6.7 ± 0.1 | −48 ± 9 | −0.94 ± 0.18 | 2 | 6.4 ± 0.22-a | −88 ± 52-a | −1.09 ± 0.062-a | 7 |
| Mepyramine | 8.7 ± 0.1 | 3 | 8.6 ± 0.1 | −44 ± 2 | −0.86 ± 0.04 | 4 | 7.9 ± 0.1 | −78 ± 1 | −0.97 ± 0.01 | 55 |
| Mizolastine | 9.1 ± 0.1 | 6 | N.D. | 8.4 ± 0.2 | −81 ± 4 | −1.00 | 3 | |||
| (+)-Terfenadine carboxylate | 7.0 ± 0.1 | 3 | N.D. | 6.9 ± 0.2 | −66 ± 1 | −0.82 ± 0.01 | 4 | |||
| (−)-Terfenadine carboxylate | 7.0 ± 0.1 | 3 | N.D. | 7.4 ± 0.4 | −68 ± 2 | −0.84 ± 0.02 | 3 | |||
| Tripelennamine | 8.0 ± 0.1 | 3 | N.D. | 7.4 ± 0.1 | −68 ± 2 | −0.84 ± 0.02 | 4 | |||
| Triprolidine | 8.5 ± 0.1 | 3 | N.D. | 8.4 ± 0.1 | −57 ± 5 | −0.71 ± 0.06 | 8 | |||
The values are expressed as means ± S.E.M. of separate experiments, each performed in triplicate.
N.D., Not determined.
↵2-a Loratadine was found to inhibit luciferase activity in the reporter-gene assay in mock transfected COS-7 cells at concentrations higher than 1 μM; therefore, the pIC50 value and the percentage inhibition of constitutive H1-receptor signaling could not be determined reliably in this assay.