Table 2.
Agonistic (pEC50) and antagonistic (pKB) activities of 1–3, 120, 121, 127, 130 and 136 at the hH2,3,4R determined in the [35S]GTPγS binding assay.[a]
|
Compound |
hH2R[b] |
hH3R[c] |
hH4R[d] |
||||||
|---|---|---|---|---|---|---|---|---|---|
|
pEC50 [e] |
E max [f] |
N |
pEC50 [e] (pKB)[g] |
E max [f] |
N |
pEC50 [e] (pKB)[g] |
E max [f] |
N |
|
|
1 |
6.01±0.07 |
1.00 |
7 |
8.52±0.10 |
1.00 |
6 |
8.20±0.08 |
1.00 |
3 |
|
2 |
5.59±0.01[h],[46] |
0.66±0.02[h],[46] |
3 |
8.12±0.10[h],[46] |
0.69±0.04[h],[46] |
3 |
8.09±0.04[h],[46] |
0.83±0.01[h],[46] |
3 |
|
3 |
6.61±0.03 |
0.33±0.03 |
5 |
(4.53±0.05) |
0 |
3 |
(3.83±0.03) |
0 |
3 |
|
120 |
6.95±0.04 |
0.66±0.01 |
3 |
(6.72±0.03) |
0 |
3 |
(3.43±0.01) |
0 |
3 |
|
121 |
7.11±0.10 |
0.22±0.01 |
3 |
5.88±0.03 |
−0.69±0.03 |
3 |
(3.75±0.01) |
0 |
3 |
|
127 |
6.86±0.03 |
0.45±0.03 |
3 |
(7.18±0.04) |
0 |
3 |
(3.38±0.01) |
0 |
3 |
|
130 |
7.28±0.10 |
0.22±0.01 |
3 |
4.46±0.02 |
−1.21±0.10 |
3 |
4.52±0.02 |
‐0.98±0.01 |
3 |
|
136 |
6.72±0.06 |
0.45±0.03 |
3 |
4.57±0.03 |
−1.20±0.15 |
3 |
4.44±0.01 |
‐0.96±0.02 |
3 |
[a]Data represent mean values ± SEM from at least three independent experiments (N), each performed in triplicate. Data were analyzed by nonlinear regression and were best fitted to sigmoidal concentration‐response curves (CRCs). [35S]GTPγS binding assay at membranes of Sf9 cells expressing [b]the hH2R plus Gsαs, [c]the hH3R plus Gαi2 plus Gβ1γ2, [d]the hH4R plus Gαi2 plus Gβ1γ2; [e]pEC50: −logEC50; [f] E max: maximal response relative to histamine (E max=1.00); [g]For determination of antagonism, reaction mixtures contained histamine (1) (100 nM) and ligands were at concentrations from 10 nM and 1 mM; pKB=−logKB. [h]Determined in a steady‐state [32P]GTPase assay on Sf9 cells expressing the related receptors.