mGlu2 and mGlu2/3 NAMs function predominantly through glutamate efficacy modulation
| MRK-8-29 | VU6001192 | MNI-137 | Decoglurant | |
|---|---|---|---|---|
| Log β (β)a | −100 (0) | −100 (0) | −0.43 ± 0.01 (0.37) | −0.62 ± 0.05 (0.24) |
| Log KB (KB)a | −6.46 ± 0.04 (347 nM) | −5.76 ± 0.04 (1.74 μM) | −6.18 ± 0.05 (661 nM) | −6.02 ± 0.08 (955 nM) |
| n | 2.6 ± 0.2 | 2.7 ± 0.3 | 8.3 ± 0.8 | 3.9 ± 0.5 |
| Basal | −2.4 ± 0.7 | 1.5 ± 1.2 | 2.9 ± 1.0 | 0.2 ± 1.4 |
| Maximum | 110.9 ± 4.4 | 124.1 ± 11.5 | 97.8 ± 1.2 | 108.9 ± 5.2 |
| Log IC50b | −6.51 ± 0.01 (307 nM) | −5.98 ± 0.02 (1.05 μM) | −5.93 ± 0.02 (1.18 μM) | −6.14 ± 0.01 (731 nM) |
↵a Data for efficacy modulation (β) and allosteric modulator affinity (KB) obtained from fitting functional data to operational model of allosterism as outlined in the Materials and Methods.
↵b Functional potencies (IC50) were obtained from interpolating data from curve fits at the EC80 glutamate concentration and plotting a concentration-response curve as outlined in the Materials and Methods.