Metabotropic Glutamate Receptor 5 - Ligands

Ligands

In addition to the orthosteric site (the site where the endogenous ligand glutamate binds) at least two distinct allosteric binding sites exist on the mGluR5. A respectable number of potent and selective mGluR5 ligands, which also comprise PET radiotracers, has been developed to date. Selective antagonists and negative allosteric modulators of mGluR5 are a particular area of interest for pharmaceutical research, due to their demonstrated anxiolytic, antidepressant and anti-addictive effects in animal studies and their relatively benign safety profile. mGluR5 receptors are also expressed outside the central nervous system, and mGluR5 antagonists have been shown to be hepatoprotective and may also be useful for the treatment of inflammation and neuropathic pain. The clinical use of these drugs may be limited by side effects such as amnesia and psychotomimetic symptoms, but these could be an advantage for some indications, or conversely mGluR5 positive modulators may have nootropic effects.