Metabotropic Glutamate Receptors: Novel Targets for Drug Development

Glutamate receptors are classified into ionotropic and metabotropic glutamate receptors (mGluRs). Ionotropic glutamate receptors form ligand-gated ion channels and, thereby, directly mediate electrical signaling of nerve cells. mGluRs indirectly regulate electrical signaling by influencing intracellular metabolic processes via G-proteins. This perspective article focuses on the mGluR family. In particular, we discuss the structure of mGluRs and their functional properties in recombinant mammalian cells. We also report on the pharmacological properties of a variety of agonists and antagonists for mGluRs and their subtype specificity. Also discussed is the physiological role of mGluRs in the CNS and their possible involvement in pathophysiological processes. It will become apparent that mGluRs are equally promising as targets for drugs modulating glutamatergic synaptic transmission as are ionotropic glutamate receptors.