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Neuroprotective Activity of Metabotropic Glutamate Receptor Ligands

  • Peter J. Flor
  • Giuseppe Battaglia
  • Ferdinando Nicoletti
  • Fabrizio Gasparini
  • Valeria Bruno
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 513)

Abstract

Metabotropic glutamate receptors form a family of currently eight subtypes (mG1uR1-8), subdivided into three groups (I-III). Activation of group-II (mGluR2 and -3) or group-III metabotropic glutamate receptors (mGluR4, -6, -7 and -8) has been established to be neuroprotective in vitro and in vivo. In contrast, group-I mGluRs (mGluR1 and -5) need to be antagonized in order to evoke protection. Initially, all neuroprotective mGluR ligands were analogues of L-glutamate. Those compounds were valuable to demonstrate protection in vitro, but showed limited applicability in animal models, particularly in chronic tests, due to low blood-brain-barrier penetration. Recently, systemically active and more potent and selective ligands became available, e.g., the group-II mGluR agonists LY354740 and LY379268 or group-I antagonists like MPEP (mGluR5-selective) and BAY36-7620 (mGluR1selective). This new generation of pharmacological agents allows a more stringent assessment of the role of individual mGluR-subtypes or groups of receptors in various nervous system disorders, including ischaemia-induced brain damage, traumatic brain injury, Huntington s and Parkinson s-like pathology or epilepsy. Moreover, the use of genetically modified animals (e.g., knock-out mice) is starting to shed light on specific functions of mGluR-subtypes in experimental neuropathologies.

Keywords

Neuroprotective Activity Cortical Culture mGluR5 Antagonist mGluR Agonist Excitotoxic Neuronal Death 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Peter J. Flor
    • 1
  • Giuseppe Battaglia
    • 2
  • Ferdinando Nicoletti
    • 2
    • 3
  • Fabrizio Gasparini
    • 1
  • Valeria Bruno
    • 2
  1. 1.Novartis PharmaAGNervous System ResearchBaselSwitzerland
  2. 2.lstituto Neurologico MediterraneoNeuromedPozzilliItaly
  3. 3.Department of Human Physiology and PharmacologyUniversity of RomeItaly

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