Physiological roles and therapeutic potential of metabotropic glutamate receptors

Abstract

Discovery of mGlu receptors has dramatically influenced our understanding of glutamatergic neurotransmission in the central nervous system. This receptor family provides a mechanism by which activation by glutamate can regulate a number of important neuronal and glial functions that are not typically modulated by ligand-gated ion channels. This includes modulation of neuronal excitability, synaptic transmission, and various metabolic functions. Because of the ubiquitous distribution of glutamatergic synapses, discovery of the mGlu receptors immediately raised the likelihood that mGlu receptors would participate in most, if not all, major functions of the CNS. In addition, the wide diversity and heterogeneous distribution of mGlu receptor subtypes could provide an opportunity for development of pharmacological agents that selectively target specific CNS systems to achieve a therapeutic effect. Over the past decade, an increasing number of agonists and antagonists selective for specific mGlu receptor subtypes have been developed. Use of these pharmacological tools along with genetic approaches has led to major advances in our understanding of the roles of mGlu receptors in regulating CNS systems and animal behavior. These studies suggest that drugs active at mGlu receptors may be useful in treatment of a wide variety of neurological and psychiatric disorders.