TABLE 5
Positive allosteric mGlu5 receptor modulators and one ligand with neutral cooperativity
Information about compound potencies in vitro in one representative assay is given as an indication only. Different assay systems were used, so potencies should be compared with caution. Because of the complexity of allosteric interactions and the different possibilities of measuring modulation, information on cooperativity is not summarized here but can be found in section III.A.2.
| Compound | Structure | Potency | Comments | References |
|---|---|---|---|---|
| I: DFB |  | EC50 = 2.6 μM | O'Brien et al., 2003 | |
| II: CPPHA |  | EC50 = 250 nM | Acts through an allosteric site distinct from the MPEP binding site | Zhao et al., 2007 |
| III: CDPPB |  | EC50 = 20 nM | Active in animal models of antipsychotic activity (e.g., PPI- or PCP-induced locomotion) | Lindsley et al., 2004; Kinney et al., 2005 |
| IV: VU-29 |  | EC50 = 11 nM | de Paulis et al., 2006 | |
| V |  | EC50 = 14 nM | Based on MPEP scaffold (pharmacological switch)! | Sharma et al., 2009 |
| VI: ADX47273 |  | EC50 = 170 nM | Active in animal models of antipsychotic activity | Liu et al., 2008 |
| VII: VU0357121 |  | EC50 = 33 nM | Interacts with a site distinct from the MPEP or CPPHA sites | Hammond et al., 2010 |
| VIII: VU0360172 |  | EC50 = 16 nM | Reverses amphetamine-induced hyperlocomotion | Rodriguez et al., 2010 |
| IX: DCB |  | IC50 = 7.6 μM (to inhibit DFB) | A derivative of DFB (I) with neutral cooperativity at mGluR5 | O'Brien et al., 2003 |
DCB, 3,3′-dichlorobenzaldazine;