Group I metabotropic glutamate receptor (Group I mGluR)

Group I metabotropic glutamate receptors (group I mGluRs) are a subgroup of the metabotropic glutamate receptor family, which are class C G protein-coupled receptors (GPCRs) composed of metabotropic glutamate receptor 1 (mGluR1, encoded by GRM1) and metabotropic glutamate receptor 5 (mGluR5, encoded by GRM5). These receptors are primarily located postsynaptically in the central nervous system and are involved in stimulating phospholipase C via Gq/G11 pathways, leading to increased diacylglycerol and inositol 1,4,5-trisphosphate, ultimately regulating protein kinase C activation and intracellular calcium release[1][2][3]. Group I mGluRs play crucial roles in modulating synaptic plasticity, neuronal excitability, and the activity of other receptors (notably NMDA receptors) and have been implicated in physiological processes such as learning, memory, and development. Dysregulation of group I mGluRs is associated with a wide range of diseases, including neurodegenerative and psychiatric disorders, cancer, epilepsy, and various pain syndromes[4][5][6]. Pharmacological modulation of these receptors (especially negative allosteric modulators of mGluR5) is under investigation for multiple CNS and cancer indications, with numerous drugs in preclinical and clinical development[2][4][6].

Other names

mGluR1/5Metabotropic glutamate receptor 1/5GRM1/GRM5 (gene symbols)Group I mGluRs

Modulation of phospholipase C-mediated pathways (via Gq/G11 proteins); Calcium signaling modulation; Modulation of NMDA receptor activity; Negative allosteric modulation (primarily mGluR5, leading to reduced excitability and neurotransmission); Inverse agonism; Positive allosteric modulation (under investigation)