Table 5: Comparison of mGlu5 NAM cooperativity (logβ) values with DHPG across different measures of receptor activity in primary mouse cortical neurons in the presence and absence of 30 µM CPCCOEt.
Data represent mean ± SEM of indicated number (n) of independent experiments performed in duplicate.
| With CPCCOEt | no CPCCOEt | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| iCa2+ (1min) | n | iCa2+ (30min) | n | IP1 accumulation | n | iCa2+ (1min) | n | iCa2+ (30min) | n | IP1 accumulation | n | |
| MPEP | full NAMa | 6 | full NAM | 5 | −0.56 ±0.11 | 11 | full NAM | 5 | full NAM | 7 | −0.55 ±0.09 | 10 |
| fenobam | full NAM | 4 | full NAM | 4 | −0.59 ±0.17 | 9 | full NAM | 4 | full NAM | 6 | −0.67 ±0.17 | 7 |
| VU0409106 | full NAM | 6 | full NAM | 5 | −0.39 ±0.09 | 10 | full NAM | 4 | full NAM | 6 | −0.52 ±0.09 | 8 |
| VU0366248 | −0.60 ±0.21 | 7 | −0.75±0.31 | 5 | n.r. | 5 | −0.36±0.15 | 5 | −0.69 ±0.09 | 5 | n.r. | 5 |
| VU0366058 | −0.59 ±0.32b | 6 | full NAM | 6 | −0.46 ±0.11 | 10 | −0.41 ±0.15 | 6 | full NAM | 6 | −0.69 ±0.20 | 8 |
| M-5MPEP | −0.65 ±0.19 | 6 | −0.88 ±0.35 | 8 | −0.24 ±0.06 | 10 | −0.31 ±0.08 | 8 | −0.80 ±0.18 | 5 | −0.33 ±0.08 | 10 |
| dipraglurant | full NAM | 5 | full NAM | 5 | full NAM | 9 | full NAM | 5 | full NAM | 6 | full NAM | 7 |
| MTEP | full NAM | 5 | full NAM | 4 | −0.52 ±0.13 | 8 | −0.68±0.16 | 5 | full NAM | 6 | −0.38 ±0.07 | 8 |
a
“full NAM” denotes complete inhibition of DHPG response, such that β values approach zero.
b
limited concentration range was tested due to compound fluorescence and therefore cannot definitively conclude cooperativity is limited.
n.r. no modulatory response was evident.