[7][8] The amino acid L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors.

Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities.

[10] Emerging research strongly points to mGluR5 playing a direct role in the pathogenesis of alcohol use disorder in humans, showing intimate involvement in the development of behavioral sensitization towards ethanol in animal models.

[12] 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[13][14][15] effects in animal studies and their relatively benign safety profile.

[16][17] 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.