Activity of H1R and H2R ligands at the hH4R The ligands were tested as described under Materials and Methods. Data shown are mean ± standard error of mean of at least three independent experiments, each performed in triplicate. pKi values were determined with [3H]histamine displacement assay; pEC50 values show the inhibition of 1 μM forskolin-induced CRE-β-galactosidase activity in SK-N-MC/hH4 cells.
pKi at hH1R | H1R Activity | pKi | pEC50 | α | |
|---|---|---|---|---|---|
| H1R liganda | |||||
| Histamine | 4.2 ± 0.1b | Agonist | 7.8 ± 0.1 | 7.7 ± 0.1 | 1 |
| 2-Methylhistamine | Agonist | 6.1 ± 0.1 | 5.9 ± 0.1 | 0.8 | |
| 2-(3-Bromophenyl)histamine | Agonist | 6.0 ± 0.1 | 5.9 ± 0.2 | 0.6 | |
| Histaprodifen | 5.7 ± 0.1d | Agonist | <5 | N.D. | N.D. |
| TEA | <4d | Agonist | <5 | N.D. | N.D. |
| PEA | 3.8 ± 0.1d | Agonist | <5 | N.D. | N.D. |
| 8R-Lisuride | 7.9 ± 0.1c | Agonist | 5.3 ± 0.1 | – | |
| Azatidine | Antagonist | <5 | N.D. | N.D. | |
| Cetirizine | 8.0 ± 0.1e | Antagonist | <5 | N.D. | N.D. |
| Clozapine | 9.4 ± 0.1f | Antagonist | 6.7 ± 0.1 | 6.8 ± 0.1 | 1 |
| Amoxapine | 7.4 ± 0.1f | Antagonist | 5.3 ± 0.1 | 6.7 ± 0.1 | 0.5 |
| Loxapine | 8.3 ± 0.1f | Antagonist | 5.4 ± 0.1 | 6.2 ± 0.1 | 0.8 |
| Octoclothepin | 8.6 ± 0.1f | Antagonist | <5 | N.D. | N.D. |
| Ebastine | 8.0 ± 0.1b | Antagonist | <5 | N.D. | N.D. |
| Fexofenadine | 8.0 ± 0.3e | Antagonist | <5 | N.D. | N.D. |
| Hydroxyzine | 8.7 ± 0.1e | Antagonist | <5 | N.D. | N.D. |
| Loratidine | 6.8 ± 0.1b | Antagonist | <5 | N.D. | N.D. |
| Mizolastine | 9.1 ± 0.1b | Antagonist | <5 | N.D. | N.D. |
| Mepyramine | 8.7 ± 0.1b | Antagonist | <5 | N.D. | N.D. |
| R-(+)-Terfenadine | 7.0 ± 0.1b | Antagonist | <5 | N.D. | N.D. |
| pKi at hH2R | H2R Activity | pKi | pEC50 | α | |
|---|---|---|---|---|---|
| H2R ligand | |||||
| Histamine | 4.3 ± 0.1g | Agonist | 7.8 ± 0.1 | 7.7 ± 0.1 | 1 |
| 4-Methylhistamine | 5.1 ± 0.1 | Agonist | 7.3 ± 0.1 | 7.4 ± 0.1 | 1 |
| Amthamine | 5.2 ± 0.1g | Agonist | 5.3 ± 0.1 | 0 | |
| Amselamine | 5.0 ± 0.1g | Agonist | 5.6 ± 0.1 | 0 | |
| Dimaprit | 4.6 ± 0.1g | Agonist | 6.5 ± 0.1 | 5.8 ± 0.2 | 0.8 |
| Impromidine | 6.3 ± 0.1g | Agonist | 7.6 ± 0.1 | 7.6 ± 0.1 | 0.5 |
| S-(+)-Sopromidine | Agonist | 5.5 ± 0.1 | 0 | ||
| R-(—)-Sopromidine | Agonist | 6.1 ± 0.1 | 0 | ||
| Aminopotentidine | 7.8 ± 0.1g | Antagonist | <5 | N.D. | N.D. |
| Burimamide | 5.4 ± 0.2g | Antagonist | 7.4 ± 0.1 | 7.7 ± 0.1 | 0.7 |
| Cimetidine | 6.2 ± 0.2g | Antagonist | <5 | N.D. | N.D. |
| Famotidine | 7.8 ± 0.1g | Antagonist | <5 | N.D. | N.D. |
| Mifentidine | Antagonist | <5 | N.D. | N.D. | |
| Ranitidine | 7.1 ± 0.1g | Antagonist | <5 | N.D. | N.D. |
| Tiotidine | 7.8 ± 0.2g | Antagonist | <5 | N.D. | N.D. |
α, intrinsic activity (1 designated for full agonistic, 0 for neutral antagonist, and —1 for full inverse agonistic activity); N.D., not determined; —, due to non-H4R-mediated effects of 8R-lisuride, the pEC50 value was not determined.
↵ a H1R antagonists astemizole, chlorpheniramine, cyproheptadine, desipramine, dexchlorpheniramine, diphenhydramine, doxepine, imipramine, ketotifen, mianserine, octoclothepin, ORG3770, promethazine, S-(—)-terfenadine, tripelennamine, and triprolidine also have pKi values <5
↵ b pKi values determined with [3H]mepyramine displacement assay (Bakker et al., 2001)
↵ c pKi value determined with [3H]mepyramine displacement assay (Bakker et al., 2004)
↵ d pKi values determined with [3H]mepyramine displacement assay (Govoni et al., 2003)
↵ e pKi values determined with [3H]mepyramine displacement assay (Gillard et al., 2002)
↵ f Potencies as inverse H1R agonists determined with receptor selection and amplification technology assay (Bakker, 2003)
↵ g pKi values determined with [125I]iodoaminopotentidine displacement assay (Leurs et al., 1994)