Table 2.
Comparison of A-841720 and prototypic mGluR1 and mGluR5 receptor antagonists, in mGluR1 and mGluR5 receptor assays
|
Mean±s.e.m. (n) |
|||||||
|---|---|---|---|---|---|---|---|
| A-841720 | LY456066 | R-214127 | CPCCOEt | MPEP | MTEP | SIB1517 | |
| Human mGluR1 FLIPRa | 10.7±3.9 | 52±6.0 | 49.7±7.2 | 14288±3017 | >10000 | >10000 | >10000 |
| (100%; n=13) | (100%; n=20) | (97%; n=10) | (82%; n=12) | (n=20) | (n=14) | (n=12) | |
| Human mGluR5 FLIPRa | 343±59.5 | >10000 | >10000 | >10000 | 29.1±5.2 | 46±8.9 | 2117±261 |
| (89%; n=13) | (n=13) | (n=10) | (n=12) | (98%; n=12) | (98%; n=16) | (99%; n=12) | |
| Rat mGluR1 Bindingb | 1.05±0.6 | 28.0±1.1 | n.d. | 11910±1644 | >10000 | >10000 | >10000 |
| (103%; n=10) | (101%; n=12) | (68%; n=3) | (n=12) | (n=12) | (n=6) | ||
| Rat mGluR1 FLIPRa | 1.0±0.2 | 10.0±2.2 | 1.8±0.3 | 5321±869 | >10000 | >10000 | >10000 |
| (96%; n=6) | (95%; n=6) | (94%; n=5) | (76%; n=3) | (n=5) | (n=5) | (n=3) | |
| Rat mGluR5 Bindingb | 200.0±17 | >10000 | >10000 | >10000 | 5.8±0.6 | 11.5±2.5 | 791.0±216 |
| (94%; n=14) | (n=4) | (n=4) | (n=7) | (110%; n=11) | (107%; n=6) | (111%; n=4) | |
Concentration–response data were generated using 10 μM L-glutamate for human mGluR1 and mGluR5 FLIPR assays, and 20 μM (S)-DHPG for rat mGluR1 FLIPR assays, respectively. Data are expressed as mean.
a
IC50 values (nM).
b
Ki values (nM)±s.e.m., and ‘n' represents the number of independent determinations.