Chapter 1. Metabotropic glutamate receptor modulators: Recent advances and therapeutic potential

Abstract

Publisher Summary This chapter discusses advances in the field of metabotropic glutamate receptor modulators and elaborates their therapeutic potential. Glutamate is considered the major excitatory neurotransmitter in the mammalian central nervous system, contributing input to the majority of excitatory synapses. Glutamatergic excitation per se is mediated by post-synaptic ion channel linked or “ionotropic” glutamate (iGlu) receptors, which include NMDA, AMPA and kainate receptor types. Metabotropic glutamate (mGlu) receptors have unique structural features that allow for multiple sites to which ligands can act to modulate receptor functions. They are characterized by a large extracellular amino terminal domain (ATD) to which glutamate binds and initiates receptor activation. This ATD region is homologous with a family of bacterial periplasmic proteins that function to transport amino acids across the bacterial cell wall. Details of classification of metabotropic glutamate receptors by “groups” are provided in the chapter. An overview of structure and modeling of mGlu receptors is presented and development of new pharmacological tools for mGlu receptors is described. Details of mGlu receptor agonists for different groups are also described.