Cpd. | Agonist | hH1R | gpH1R | Pot. Rat. gp/h | hH1R-F153L/I433V | Pot. Rat. m/h | gp-ileum | Pot. Rat. rec/il | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
EC50 | Rel. Pot. | Emax | EC50 | Rel. Pot. | Emax | EC50 | Rel. Pot. | Emax | Rel. Pot. | |||||||||||
μM | μM | μM | ||||||||||||||||||
1 | Histamine | 0.184 ± 0.094 | 100 | 1.00 | 0.220 ± 0.047 | 100 | 1.00 | 0.84 | 0.163 ± 0.029 | 100 | 1.00 | 1.13 | 100 | 1.00 | ||||||
2 | 2-Methylhistamine | 0.837 ± 0.110 | 22.0 | 0.98 ± 0.03 | 0.708 ± 0.181 | 31.1 | 0.97 ± 0.04 | 0.87 | N.D. | N.D. | N.D. | N.D. | 14.0 | 2.22 | ||||||
3 | 2-(2-Thiazolyl)ethanamine | 0.440 ± 0.116 | 41.8 | 0.97 ± 0.13 | 0.433 ± 0.133 | 50.8 | 1.00 ± 0.08 | 1.02 | 0.373 ± 0.076 | 43.7 | 1.08 ± 0.05* | 1.17 | 45.0 | 1.13 | ||||||
4 | Betahistine | 1.438 ± 0.368 | 12.8 | 0.86 ± 0.10 | 0.963 ± 0.277 | 22.8 | 0.86 ± 0.09 | 1.49 | N.D. | N.D. | N.D. | N.D. | 8.0 | 2.85 | ||||||
5 | 2-Benzylhistamine | 6.518 ± 0.482 | 2.80 | 0.75 ± 0.10 | 5.234 ± 1.432 | 4.20 | 0.88 ± 0.11 | 1.24 | 3.130 ± 0.060* | 5.21 | 0.74 ± 0.01 | 2.08 | 2.5 | 1.68 | ||||||
6 | 2-Phenylhistamine | 0.877 ± 0.201 | 21.0 | 0.79 ± 0.07 | 0.160 ± 0.010* | 137.5 | 0.98 ± 0.09* | 5.48 | 0.638 ± 0.100 | 25.5 | 0.91 ± 0.06 | 1.37 | 31.0 | 4.44 | ||||||
7 | 2-(3-Methylphenyl)histamine | 1.088 ± 0.240 | 17.0 | 0.77 ± 0.11 | 0.134 ± 0.065* | 164.2 | 0.89 ± 0.05 | 8.06 | N.D. | N.D. | N.D. | N.D. | 14.7 | 11.2 | ||||||
8 | 2-(2-Fluorophenyl)histamine | 2.783 ± 1.092 | 6.6 | 0.71 ± 0.04 | 0.766 ± 0.231* | 28.9 | 0.88 ± 0.14* | 3.66 | N.D. | N.D. | N.D. | N.D. | 5.8 | 4.98 | ||||||
9 | 2-(3-Fluorophenyl)histamine | 0.683 ± 0.303 | 26.9 | 0.75 ± 0.04 | 0.073 ± 0.022* | 301.4 | 0.89 ± 0.08* | 9.39 | 0.263 ± 0.079 | 62.0 | 0.85 ± 0.09 | 2.60 | 85.0 | 3.55 | ||||||
10 | 2-(4-Fluorophenyl)histamine | 3.220 ± 0.569 | 5.5 | 0.60 ± 0.12 | 0.587 ± 0.127* | 37.5 | 0.80 ± 0.07* | 5.65 | N.D. | N.D. | N.D. | N.D. | 12.5 | 3.00 | ||||||
11 | 2-(3,5-Difluoro-phenyl)histamine | 0.765 ± 0.133 | 24.0 | 0.59 ± 0.10 | 0.132 ± 0.029* | 166.7 | 0.83 ± 0.11* | 5.80 | N.D. | N.D. | N.D. | N.D. | 15.0 | 11.1 | ||||||
12 | 2-(3-Chlorophenyl)histamine | 0.434 ± 0.128 | 42.4 | 0.71 ± 0.05 | 0.081 ± 0.026* | 271.6 | 0.89 ± 0.10* | 5.35 | 0.160 ± 0.056* | 101.9 | 0.81 ± 0.08* | 2.71 | 96.0 | 2.83 | ||||||
13 | 2-(4-Chlorophenyl)histamine | 16.440 ± 3.880 | 1.1 | 0.54 ± 0.11 | 2.313 ± 0.788* | 9.5 | 0.56 ± 0.11 | 7.11 | N.D. | N.D. | N.D. | N.D. | 0.5 | 19.0 | ||||||
14 | 2-(3-Bromophenyl)histamine | 0.210 ± 0.065 | 87.6 | 0.73 ± 0.01 | 0.053 ± 0.002* | 415.1 | 0.95 ± 0.11* | 3.96 | 0.143 ± 0.032 | 114.0 | 0.75 ± 0.05 | 1.47 | 112 | 3.71 | ||||||
15 | 2-(3-Iodophenyl) histamine | 0.220 ± 0.118 | 83.6 | 0.70 ± 0.08 | 0.040 ± 0.021* | 550.0 | 0.86 ± 0.05* | 5.50 | 0.133 ± 0.051 | 122.6 | 0.70 ± 0.09 | 1.65 | 96.0 | 5.73 | ||||||
16 | 2-(3-Methoxyphenyl)histamine | 0.262 ± 0.100 | 70.2 | 0.74 ± 0.05 | 0.060 ± 0.017* | 366.7 | 1.00 ± 0.09* | 4.37 | N.D. | N.D. | N.D. | N.D. | 42.1 | 8.71 | ||||||
17 | 2-(3-Trifluoromethylphenyl) histamine | 0.243 ± 0.091 | 41.8 | 0.74 ± 0.04 | 0.057 ± 0.023* | 386.0 | 0.91 ± 0.12* | 4.26 | N.D. | N.D. | N.D. | N.D. | 129 | 2.99 | ||||||
18 | 2-(4-Methylphenylthiomethyl) histamine | 2.54 ± 0.36 | 7.2 | 0.50 ± 0.05 | 0.77 ± 0.18* | 29.9 | 0.80 ± 0.11* | 3.18 | N.D. | N.D. | N.D. | N.D. | 12.7 | 2.35 | ||||||
19 | Methylhistaprodifen | 0.068 ± 0.018 | 270.5 | 0.77 ± 0.10 | 0.019 ± 0.006* | 1157.8 | 0.87 ± 0.06 | 3.57 | 0.040 ± 0.011 | 407.5 | 0.88 ± 0.06 | 1.70 | 343 | 3.38 | ||||||
20 | Dimethylhistaprodifen | 0.100 ± 0.026 | 184.0 | 0.64 ± 0.09 | 0.027 ± 0.012* | 814.8 | 0.84 ± 0.06* | 3.70 | 242 | 3.37 | ||||||||||
21 | Pyrrolidinohistaprodifen | 0.293 ± 0.120 | 62.8 | 0.19 ± 0.02 | 0.044 ± 0.013* | 500.0 | 0.40 ± 0.03* | 6.66 | 0.258 ± 0.217 | 63.2 | 0.34 ± 0.05 | 1.14 | 67.0 | 7.46 | ||||||
22 | Nα-(Imidazolylethyl)histaprodifen | 0.238 ± 0.138 | 77.3 | 0.84 ± 0.08 | 0.050 ± 0.025* | 440.0 | 0.89 ± 0.09 | 4.76 | N.D. | N.D. | N.D. | N.D. | 3630 | 0.12 | ||||||
23 | Dimeric histaprodifen | 0.653 ± 0.210 | 28.2 | 0.65 ± 0.11 | 0.066 ± 0.033* | 333.3 | 0.92 ± 0.08* | 9.85 | N.D. | N.D. | N.D. | N.D. | 1680 | 0.20 | ||||||
46 | Amthamine | — | — | 0.01 ± 0.02 | 150 ± 56 | — | 0.14 ± 0.05* | — | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. | ||||||
47
| Dimaprit | — | — | 0.06 ± 0.04 | — | — | 0.06 ± 0.03 | — | N.D. | N.D. | N.D. | N.D. | N.D. | N.D. |
N.D., not determined; —, not applicable because stimulatory effects of agonists were too small; Cpd., compound.
↵ * P < 0.05 for comparison of hH1R versus other H1R constructs