Table 1.
Human histamine H3 receptor affinity and human MAO B inhibition of tested compounds 5–31 and DL76.
| Compounds | R | n | H3R a Ki (nM) (95%CI) |
MAO B b IC50 (nM) (%Inh.) c |
MAO A b IC50 (nM) (%Inh.) d |
|---|---|---|---|---|---|
| 5 |
|
1 | 371 (136, 1009) |
2.7 ± 0.4 | nt e |
| DL76 |
|
1 | 38 f (8, 181) |
48 ± 15 | >10,000 (9%) |
| 6 | 2 | 309 (166, 574) |
290 ± 7 | >10,000 (10%) |
|
| 7 | 3 | 252 (64, 990) |
(28%) | nt e | |
| 8 | 4 | 225 (98, 519) |
(13%) | nt e | |
| 9 |
|
1 | 69 (49, 96) |
11 ± 1 | >10,000 (5%) |
| 10 | 2 | 153 (46, 505) |
475 ± 38 | >10,000 (2%) |
|
| 11 | 3 | 1556 (349, 6941) |
(36%) | nt e | |
| 12 |
|
1 | 98 (43, 226) |
117 ±12 | >10,000 (10%) |
| 13 | 2 | 102 (18, 571) |
1405 ± 494 | nt e | |
| 14 | 3 | 114 (33, 397) |
(33%) | nt e | |
| 15 | 4 | 351 (223, 552) |
(13%) | nt | |
| 16 |
|
1 | 1624 (1075, 2453) |
476 ± 38 | >10,000 (6%) |
| 17 | 2 | 3437 (2701, 4374) |
(38%) | nt e | |
| 18 | 3 | 3535 (2528, 4942) |
2777 ± 66 | >10,000 (19%) |
|
| 19 | 4 | 2575 (542, 12227) |
1953 ± 45 | >10,000 (24%) |
|
| 20 |
|
1 | 341 (49, 2388) |
(37%) | nt e |
| 21 | 2 | 1381 (923, 2066) |
(35%) | nt e | |
| 22 | 3 | 2235 (1136, 4397) |
(41%) | nt e | |
| 23 | 4 | 2083 (936, 4637) |
(34%) | nt e | |
| 24 |
|
1 | 316 (123, 808) |
(37%) | nt e |
| 25 | 2 | 400 (152, 1050) |
(33%) | nt e | |
| 26 | 3 | 531 (344, 822) |
(39%) | nt e | |
| 27 | 4 | 1350 (651, 2798) |
(10%) | nt e | |
| 28 |
|
1 | 111 (68, 180) |
45 ± 4 | >10,000 (10%) |
| 29 | 2 | 299 (105, 855) |
1627 ± 78 | >10,000 (23%) |
|
| 30 | 3 | 324 (121, 870) |
(18%) | nt e | |
| 31 | 4 | 829 g (313, 2194) |
(23%) | nt e | |
| rasagiline | nt e | 15 ± 1 | nt e | ||
| pargiline | nt e | 360 ± 138 | nt e | ||
| safinamide | nt e | 7.7 ± 1.2 | nt e | ||
| clorgiline | nt e | nt e | 1.76 ± 0.5 nM | ||
a [3H]Nα-Methylhistamine-binding assay in HEK293 cells stably expressing the human H3R; mean value within the 95% confidence interval (CI); b fluorometricAmplex™ Red MAO assay [15]; mean ± SEM of 2–5 independent experiments; c the percent of inhibition at 1 μM, mean values of two independent experiments; d the percent of inhibition at 10 μM, mean values of two independent experiments; e nt = not tested; f Ki (±SEM) = 22 ± 3 nM in [125I]Iodoproxyfan binding assay in CHO K1 cells, data from Reference [13]; g data from Reference [16].