Editorial [Hot Topic: Metabotropic Glutamate Receptors: Medicinal Chemistry and Therapeutic Implications (Guest Editor: Craig W. Lindsley)]

Glutamate (glutamic acid) is the major excitatory neurotransmitter in the mammalian CNS, exterting its modulatory effects through either ionotropic or metabotropic glutamate receptors (mGluRs). The mGluRs are family C G-protein coupled receptors, characterized by a large extracellular amino-terminal agonist binding site. Eight mGluRs have been cloned, sequenced and assigned to three groups based on their structure, coupling to effector mechanisms and pharmacology. Group I mGluRs (mGluR1 and mGluR5) are postsynaptic receptors while Group II (mGluR2 and mGluR3) and Group III (mGluR6, mGluR7 and mGluR8) are located presynaptically. Dysfunction in glutaminergic systems has been implicated in a number of neurological and psychiatric disorders including pain, addiction, Parkinson's disease, anxiety and schizophrenia. Recent studies suggest that small molecules capable of modulating mGluR activity will have broad applicability for the treatment of a variety of CNS pathologies. This issue contains a collection of reviews covering cutting-edge biology and medicinal chemistry for all 8 mGluR subtypes as well as a general introduction to this nacsent field. Importantly, the reviews describe the discovery and development of selective agonists, antagonists and allosteric modulators (both positive and negative) that target individual mGluR subtypes. The authors have included background biology relevant to understanding the target(s) for therapeutic intervention, lead discovery and progress towards target validation in various electrophysiological and animal behavioral models. I would like to thank the authors for their hard work, dedication and excellent, comprehensive contributions to this special issue of Currents Topics in Medicinal Chemistry. Our hope is that this issue will serve as a key reference work for those engaged in, or interested in, metabotropic gluatmate receptors and the various strategies employed to modulate this class of GPCRs for a number of therapeutic implications.