Targeting metabotropic glutamate receptors in the treatment of epilepsy: rationale and current status

Abstract

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Spike‐wave discharges in absence epilepsy: segregation of electrographic components reveals distinct pathways of seizure activity

“…Of note, cortical 5-9 Hz oscillations have also been recorded in non-epileptic control (NEC) rats (Pinault et al 2001;Pinault, 2003;Pinault & O'Brien, 2005). A number of specific epileptogenic alterations might explain why these oscillations lead to SWDs in GAERS but not NEC rats, including alterations in voltage-gated ion channels, such as T-type calcium or HCN channels, as well as in GABA A receptors and metabotropic glutamate receptors (Luhmann et al 1995;Tsakiridou et al 1995;Kim et al 2001;Klein et al 2004;Strauss et al 2004;Budde et al 2005;Kole et al 2007;Cope et al 2009;Schofield et al 2009;McCafferty et al 2018;Celli et al 2019). Furthermore, the cortical 5-9 Hz oscillations may also differ in GAERS and NEC rats.…”

Do Mast Cells Have a Role in Tendon Healing and Inflammation?

“…It acts by binding to various glutamate receptors, subdivided into metabotropic and ionotropic types. The metabotropic glutamate receptors are G protein-linked and include the group I (mGlu1R and mGlu5R; coupled to Gq/G11 proteins), group II (mGlu2 and mGlu3; coupled to Gi/Go proteins), and Group III (mGlu4, mGlu6, mGlu7 and mGlu8 receptors; coupled to Gi/Go proteins) metabotropic receptors [118][119][120]. The ionotropic glutamate receptors are ion channel-linked and are grouped into four distinct classes based on pharmacology and structural homology: the NMDA receptors (NMDAR1, NMDAR2A-NMDAR2D, NMDAR3A, NMDAR3B) [121][122][123][124], the AMPA receptors (GluA1-GluA4) [125,126], the kainate receptors (GluK1-5) [127,128], and the δ receptors (GluD1 and GluD2) [122].…”

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“…Hyperactivation of the NMDA receptors by extracellular excitatory amino acids like glutamate implicated in the cellular events leading to neuronal death and decline in function following traumatic or ischemic brain injury [75][76] . Agents modulating glutamate transmission were developed, targeting as antagonists to NMDA receptors [77][78][79] , that could theoretically ameliorate the harmful effects of excessive glutamate. Based on the location of the CB1 receptors on presynaptic terminals of glutamatergic synapses and the inhibitory nature of their signaling, eCBs and other CB1 agonists as neuromodulators of glutamate releases, as modulators of excitotoxicity continuing numerous brain disorders.…”