Metabotropic glutamate receptors and their ligands applications in neurological and psychiatric disorders

Metabotropic glutamate receptors (mGluRs) consist of a large family of G-protein coupled receptors that are critical for regulating normal neuronal function in the central nervous system. The wide distribution and diverse physiological roles of various mGluR subtypes make them highly attractive targets for the treatment of a number of neurological and psychiatric disorders. The discovery of subtype selective ligands for these receptors has provided the tools to support a number of preclinical studies, suggesting the numerous therapeutic potential that lies in the ability selectively to modulate a specific mGluR subtype. mGluRs do not activate ion channels directly but instead through G-protiens activate second messenger mechanisms in the neurons. So far 8 subtypes of mGluRs have been identified which divided into three groups (Group I, II, and III) according to their sequence similarities, Signal transduction mechanisms and pharmacological properties. Depending on the receptor subtype, they might be localized at presynaptic or postsynaptic sites which regulate glutamate and other neurotransmitters release. As I applied many mGluR ligands on hippocampal slices and observed interesting results on synaptic transmission and modulation of certain neurotransmitters such as adenosine, I intended to study their application in neurological diseases. The method was based on my experiences from researches and different seminars to evaluate last decade development on mGluRs and their ligands application in certain neurological disorders. Therefore, aim of this review article is to describe mGluRs and their role in the excitotoxicity and neuroprotection. Then, application of different mGluR ligands for the treatment of a variety of neurological disorders including schizophrenia, Parkinson's disease, anxiety disorders, epilepsy, and drug abuse has been described.