Group I mGlu Receptor Antagonists In addition to (S)-MCPG, it's parent compound, (S)-4-CPG is also a widely used group I mGlu receptor antagonist. Like (S)-MCPG, this compound is a competitive antagonist but has a greater degree of selectivity for mGlu1 receptors over mGlu5 receptors. Indeeed, in many studies it has been inactive at mGlu5 receptors, although the usefulness of (S)-4-CPG in neurons is limited by a weak agonist action at group II mGlu receptors. However, the 2-methyl derivative of (S)-4-CPG, 4C2MCPG (LY367385), has a higher potency and selectivity for mGlu1 receptors over mGlu5 receptors, with no effects on group II receptors. Hence, 4C2MCPG is the competitive antagonist of choice for the study of the physiological roles mGlu 1 receptors play in the CNS. The only competitive antagonist of mGlu5 receptors developed to date is the recently reported LY344545. This compound shows an eight-fold selectivity for mGlu5 receptors over mGlu1 receptors, although strong effects ate group II receptors ande weak NMDA receptor antagonist activity will probably resirict the usefullness of this compound. Other developments have led to the synthesis of selective non-competitive antagonists of the group I mGlu receptors. CPCCOEt, selectively antagonises mGlu1 receptors while MPEP is a highly potent mGlu5 receptor antagonist. These two compounds are likely to be widely used in the analysis of the functional roles of the group I mGlu receptors.

Group II mGlu Receptor Antagonists The group II mGlu receptor antagonist with the highest potency is currently LY341495, which acts at these receptors in the nanomaloar range. Indeed, LY341495 has recently been radiolabelled for radioligand binding studies. Although this compound acts at all other mGlu receptors (click here), its affinity for the group II receptors (~1 nM) will make it the antagonist of choice. Othe useful antagonists of group II mGlu receptors are ADED and EGlu, an ethyl- substituted L-glutamate analogue. Although less potent than LY341495, both EGlu and ADED are inactive at group I and group III receptors. Finally, (S)-MCPG is still widely used to study the physiological roles of the group II mGlu receptors.