Perhaps most importantly, glutamatergic receptors include multiple modulatory sites that are actively being studied as potential treatment targets. Receptors for glutamate are divided into two broad families, ionotropic and metabotropic. Ionotropic receptors are differentiated based upon sensitivity to the synthetic glutamate derivatives NMDA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), and kainate. In particular, NMDA receptors contain several allosteric modulatory sites that are treatment targets, including a site for the endogenous brain amino acids glycine and D-serine (Fig. 1) and a redox site that is sensitive to glutathione (GSH). Metabotropic receptors, which are G protein coupled and mediate longer-term neuromodulatory effects of glutamate, are divided into groups on the basis of effector coupling and ligand sensitivity.
