Metabotropic glutamate receptors (mGluR) function to modulate excitatory synaptic transmission in the brain. Eight subtypes (1-8) and multiple splice variants of the mGluR have been identified and grouped based on their pharmacological properties. Group I mGluRs (subtypes 1 and 5) activate the phosphatidyl inositol pathway, while Group II (2 and 3) and Group III (4, 6, 7, and 8) inhibit adenylyl cyclase. L-AP4, an analog of L-glutamic acid, is a selective Group III mGluR agonist that functions presynaptically to suppress glutamate release (IC50 = 2.5 μM). L-AP4 has been shown to depress synaptic transmission in glutamatergic pathways in the hippocampus, olfactory bulb, and retina as well as act as an agonist at the quisqualate-sensitized AP6 site in hippocampus.
