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Neuroprotective Activity of Metabotropic Glutamate Receptor Ligands

  • Chapter
Molecular and Cellular Biology of Neuroprotection in the CNS

Part of the book series: Advances in Experimental Medicine and Biology ((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.

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Authors and Affiliations

  1. Novartis PharmaAG, Nervous System Research, Basel, Switzerland

    Peter J. Flor & Fabrizio Gasparini

  2. lstituto Neurologico MediterraneoNeuromed, Pozzilli, Italy

    Giuseppe Battaglia, Ferdinando Nicoletti & Valeria Bruno

  3. Department of Human Physiology and Pharmacology, University of Rome, Italy

    Ferdinando Nicoletti

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  1. Peter J. Flor
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  2. Giuseppe Battaglia
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  3. Ferdinando Nicoletti
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  4. Fabrizio Gasparini
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  5. Valeria Bruno
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  1. Institute of Physiology, University of Kiel, Kiel, Germany

    Christian Alzheimer

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Flor, P.J., Battaglia, G., Nicoletti, F., Gasparini, F., Bruno, V. (2003). Neuroprotective Activity of Metabotropic Glutamate Receptor Ligands. In: Alzheimer, C. (eds) Molecular and Cellular Biology of Neuroprotection in the CNS. Advances in Experimental Medicine and Biology, vol 513. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0123-7_7

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