The promiscuous mGlu5 receptor – a range of partners for therapeutic possibilities?

The issue of non-specific effects for potential therapeutics is particularly salient in neurological/psychiatric disorders, where adverse drug reactions could impair critical brain functions. The issue of specificity is not limited to candidate molecules, as receptor targets themselves often influence physiological as well as pathological outcomes. Metabotropic glutamate receptor 5 (mGlu5) is an example of a “promiscuous” receptor target that has been implicated in addiction, but also many other processes. However, if receptor modulation could be restricted to specific pathways/brain regions, mGlu5 may still prove to be a viable therapeutic target for various indications. Using this premise, a number of possible methods to refine drug development strategy are discussed, including exploiting specific interactions of mGlu5 with other receptors to narrow the influence of pharmacological agents, and also the use of RNA interference targeted to specific cells/regions of the brain.