Table 3.
Chemical structures and binding affinities of analogues 5e-m at native iGluRs (rat synaptosomes) and homomeric recombinant iGluRs. All values in μM.a
 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Native iGluRs (synaptosomes)b | Cloned homomeric iGluRsc | ||||||||
| AMPA IC50 | KA IC50 | NMDA Ki | GluA1 Ki | GluA2 Ki | GluK1 Ki | GluK2 Ki | GluK3 Ki | ||
| 5e |  |
40 [4.40±0.05] | 20 [4.71±0.05] | 3.8 [5.42±0.01] | 19 | 55 | 20 ± 1.8 | >100 | 6.4 ± 0.41 |
| 5f |  |
29 [4.57±0.13] | 23 [4.65±0.03] | 3.1 [5.51±0.02] | 15 | 40 | 25 ± 1.2 | >100 | 5.9 ± 0.62 |
| 5g |  |
27 [4.581±0.07] | 25 [4.61±0.05] | 1.7 [5.76±0.01] | 12 | 33 | 22 ± 2.3 | >100 | 6.5 ± 0.92 |
| 5h |  |
59 [4.30±0.13] | >100 | 10 [4.98±0.01] | 22.7 | 82.9 | 100 | 100 | 13 ± 0.17 |
| 5i |  |
13 [4.92±0.13] | >100 | 4.1 [5.39±0.03] | 10 | 56 | 76 ± 1.8 | >100 | 16 ± 0.98 |
| (±)-5j | -NH2 | 52 [4.29±0.07] | 86 [4.07±0.04] | 14 [4.87±0.05] | -- | -- | 32.7 ± 7 | >100 | 19.3 ± 0.9 |
| (±)-5k |  |
23 [4.65±0.09] | >100 | 15 [4.82±0.03] | -- | -- | 19 ± 2.8 | 19c | 10.9 ± 0.5 |
| (±)-5l |  |
27 [4.57±0.04] | >100 | 36 [4.46±0.08] | -- | -- | 27.6 ± 0.6 | ∼100 | 14.0 ± 0.9 |
| (±)-5m |  |
24 [4.63±0.04] | 16 [4.81±0.03] | 6.9 [5.16±0.04] | -- | -- | 18.5 ± 1.8 | ∼100 | 3.95 ± 0.2 |
a
-,--: Values not determined, Radio ligands used: AMPA, [3H]AMPA; KA, [3H]KA; [3H]CGP-39653; GluA1, [3H]AMPA; GluA2, [3H]AMPA]; GluK1, [3H]NF608; GluK2 and GluK3, [3H]KA
b
Data are mean values of three to six individual experiments performed in triplicate. For AMPA and KA: pIC50 values with SEM in brackets. For NMDA: pKi values with SEM in brackets.
c
Mean values ± SEM of at least three experiments conducted in triplicate at 12–16 drug concentrations.
c
n=1.