Neuroprotective Activity of Metabotropic Glutamate Receptor Ligands

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