Activity of SIB-1757 and SIB-1893 on recombinant ionotropic glutamate receptors
| Receptor Subtype | Agonist Activity (EC50) | Antagonist Activity (IC50) | ||||
|---|---|---|---|---|---|---|
| Glutamate | SIB-1757 | SIB-1893 | CNQX | SIB-1757 | SIB-1893 | |
| μM | ||||||
| AMPA receptors | ||||||
| hGluR1i | 14.4 | >30 | >30 | 2.2 | >30 | >30 |
| (8.7, 23.9) | (2.0, 2.6) | |||||
| hGluR1i/GluR2i(R) | 3.8 | >30 | >30 | 2.9 | >30 | >30 |
| (2.2, 6.5) | (1.5, 5.9) | |||||
| hGluR2i(Q) | 5.3 | >30 | >30 | 1.2 | >30 | >30 |
| (3.6, 7.7) | (0.6, 2.4) | |||||
| hGluR3i | 26.3 | >30 | >30 | 2.6 | >30 | >30 |
| (18.3, 37.6) | (1.9, 3.6) | |||||
| hGluR4i(G) | 18.7 | >30 | >30 | 4.6 | >30 | >30 |
| (12.3, 28.5) | (4.0, 5.4) | |||||
| Kainate receptors | ||||||
| hGluR5-2 | 58 | >30 | >30 | 13.6 | >30 | >30 |
| (33.1, 104) | (5.2, 35.4) | |||||
| hGluR6(I,Y,Q) | 15.4 | >30 | >30 | 8.0 | >30 | >30 |
| (5.8, 41.6) | (3.7, 16.9) | |||||
| NMDA receptors | MK-801 | |||||
| hNMDAR1A/2A | 0.71 | >30 | >30 | 1.3 | >30 | >30 |
| (0.26, 1.9) | (0.8, 2.1) | |||||
| hNMDAR1A/2B | 0.48 | >30 | >30 | 0.5 | >30 | >30 |
| (0.26, 0.87) | (0.3, 0.8) | |||||
Activity of SIB-1757 and SIB-1893 was examined on recombinant glutamate receptors stably expressed in cell lines using Ca2+measurements. For agonist activity determinations (EC50values), SIB-1757 and SIB-1893 were tested alone, and for the antagonist tests (IC50 values), the compounds were tested in the presence of an ∼EC80 value of glutamate. The EC50values for glutamate and the IC50 values for CNQX or MK-801 are reported for each receptor subtype, expressed as the geometric mean (lower, upper S.D.). Data for SIB-1757 and SIB-1893 represent the average of two to four separate determinations.