Metabotropic Glutamate Receptors: A Review on Prospectives and Therapeutic Aspects

Ankur      Vaidya; Shweta      Jain; Abhishek   K.   Jain; Abhinav      Agrawal; Sushil   K.   Kashaw; Sanjay   K.   Jain; Ram   K.   Agrawal

doi:10.2174/1389557511313130010

Abstract

The metabotropic glutamate (mGluRs) receptors are a distinct class of G-protein-coupled receptors that act through activation of phospholipase C and/or inhibition of adenylate cyclase. They encompass seven-transmembrane domain proteins, comprehensively expressed in neuronal and glial cells within the brain, spinal cord and periphery and are involved in controlling pathophysiology of a number of diseases. These receptors may be sorted into three groups based on similarity of amino acid sequence, pharmacology and the transducer pathways they couple. The agonists and antagonists act at the N-terminal glutamate binding site and present a pharmacological strategy to modulate pathogenesis. A number of these compounds are positive or negative allosteric modulators that bind within the receptor transmembrane heptahelical domains. This imparts improved subtype selectivity, improved bioavailability and better drug like properties (e.g. CNS penetration). The mGluRs are presently the focal point of sizeable attention because of their potential as drug targets for the treatment of neurological and psychiatric disorders of the brain including Schizophrenia, Alzheimer’s disease, Parkinson’s disease, addiction, anxiety, depression, epilepsy and pain. The present review focuses on signal transduction mechanisms implicated to control and functionally upregulate the glutamatergic transmission system. The article also hallmarks agonists and antagonists for mGluRs as pivotal agents to ameliorate an array of neurological and psychiatric disorders.

Keywords: Glutamate, Metabotropic glutamate, CNS, Parkinsonism, anxiety.

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