Overview Central & Peripheral Nervous Systems: Metabotropic glutamate receptors

Abstract

Metabotropic glutamate (mGlu) receptors are becoming increasingly interesting as potential drug targets for the treatment of a variety of central nervous system (CNS) disorders including epilepsy and chronic and acute neurodegeneration. In contrast to the ionotropic glutamate (iGlu) receptors of the N-methyl-D-aspartate (NMDA), 2-amino-3-[5-methyl-3-hydroxyisoxazol-4-yl]propionic acid (AMPA) and kainate types that form ion channels, mGlu receptors couple to G-proteins and modulate a variety of membrane enzymes and ion channels. The eight mGlu receptor subtypes revealed to date by molecular cloning exhibit not only distinct pharmacological properties, but also different functions in the brain. This article describes the potential disease targets of compounds acting at the various mGlu receptor subtypes, and the development of such compounds by reviewing both the primary and patent literature.

Key Words:

• central nervous system
• G-protein coupled receptors
• epilepsy
• stroke
• neurodegeneration
• metabotropic glutamate receptors