Metabotropic glutamate receptor 2

Available structures
PDBOrtholog search: PDBe RCSB
Aliases GRM2, GLUR2, GPRC1B, MGLUR2, mGlu2, glutamate metabotropic receptor 2
External IDs MGI: 1351339 HomoloGene: 20229 GeneCards: GRM2
Targeted by Drug
DCG-IV, eglumetad, LY379268, Ro4491533, 4-MPPTS, biphenylindanone A, CBiPES[1]
RNA expression pattern
More reference expression data
Species Human Mouse









RefSeq (mRNA)



RefSeq (protein)



Location (UCSC) Chr 3: 51.71 – 51.72 Mb Chr 9: 106.64 – 106.66 Mb
PubMed search [2] [3]
View/Edit HumanView/Edit Mouse

Metabotropic glutamate receptor 2 is a protein that in humans is encoded by the GRM2 gene.[4][5]


L-glutamate is the major excitatory neurotransmitter in the central nervous system and activates both ionotropic and metabotropic glutamate receptors. Glutamatergic neurotransmission is involved in most aspects of normal brain function and can be perturbed in many neuropathologic conditions. The metabotropic glutamate receptors are a family of G protein-coupled receptors, that have been divided into 3 groups on the basis of sequence homology, putative signal transduction mechanisms, and pharmacologic properties. Group I includes GRM1 and GRM5 and these receptors have been shown to activate phospholipase C. Group II includes GRM2 (this receptor) and GRM3 while Group III includes GRM4, GRM6, GRM7 and GRM8. Group II and III receptors are linked to the inhibition of the cyclic AMP cascade but differ in their agonist selectivities.[5]

Role in hallucinogenesis

Many psychedelic drugs (e.g. LSD-25) produce their effects by binding to the oligomerized complexes of the 5HT2A and mGlu2 receptors.[6][7] Lisuride acts preferentially or exclusively on the non-heteromerized 5HT2A receptors, which are not capable of inducing psychedelic effects. Due to this, lisuride is capable of reducing the hallucinogenic effects of these drugs through competitive agonistic activity (producing the effect of a silent-agonist in the presence of these drugs).

Strong agonists for either subunit of the 5HT2A-mGlu2R heterocomplex suppress signaling through the partner subunit and inverse agonists for either subunit potentiate the signaling through the partner subunit.


The development of subtype-2-selective positive allosteric modulators (PAMs) experienced steady advance in recent years.[8] mGluR2 potentiation is a new approach for the treatment of schizophrenia.[9][10] On the other hand, antagonists and negative allosteric modulators of mGluR2/3 have potential as antidepressant drugs.[11][12][13][14]



Highly selective mGluR2 PAM (2010),[16] analog of BINA



Protein–protein interactions

The metabotropic glutamate receptor 2 is able to form a heteromeric complex with its isoform mGluR4. This heteromer exhibits a pharmacological profile distinct from the parent receptor monomers.[33]

See also


  1. "Drugs that physically interact with Metabotropic glutamate receptor 2 view/edit references on wikidata".
  2. "Human PubMed Reference:".
  3. "Mouse PubMed Reference:".
  4. Flor PJ, Lindauer K, Püttner I, Rüegg D, Lukic S, Knöpfel T, Kuhn R (April 1995). "Molecular cloning, functional expression and pharmacological characterization of the human metabotropic glutamate receptor type 2". The European Journal of Neuroscience. 7 (4): 622–9. doi:10.1111/j.1460-9568.1995.tb00666.x. PMID 7620613.
  5. 1 2 "Entrez Gene: GRM2 glutamate receptor, metabotropic 2".
  6. Moreno JL, Miranda-Azpiazu P, García-Bea A, Younkin J, Cui M, Kozlenkov A, Ben-Ezra A, Voloudakis G, Fakira AK, Baki L, Ge Y, Georgakopoulos A, Morón JA, Milligan G, López-Giménez JF, Robakis NK, Logothetis DE, Meana JJ, González-Maeso J (2016). "Allosteric signaling through an mGlu2 and 5-HT2A heteromeric receptor complex and its potential contribution to schizophrenia". Science Signaling. 9 (410): ra5. doi:10.1126/scisignal.aab0467. PMID 26758213.
  7. Baki L, Fribourg M, Younkin J, Eltit JM, Moreno JL, Park G, Vysotskaya Z, Narahari A, Sealfon SC, Gonzalez-Maeso J, Logothetis DE (January 2016). "Cross-signaling in metabotropic glutamate 2 and serotonin 2A receptor heteromers in mammalian cells". Pflugers Archiv. 468: 775–93. doi:10.1007/s00424-015-1780-7. PMID 26780666.
  8. Fraley ME (September 2009). "Positive allosteric modulators of the metabotropic glutamate receptor 2 for the treatment of schizophrenia". Expert Opinion on Therapeutic Patents. 19 (9): 1259–75. doi:10.1517/13543770903045009. PMID 19552508.
  9. Conn PJ, Jones CK (January 2009). "Promise of mGluR2/3 activators in psychiatry". Neuropsychopharmacology. 34 (1): 248–9. doi:10.1038/npp.2008.156. PMC 2907744Freely accessible. PMID 19079073.
  10. Muguruza, Carolina; Meana, J. Javier; Callado, Luis F. (2016). "Group II Metabotropic Glutamate Receptors as Targets for Novel Antipsychotic Drugs". Frontiers in Pharmacology. 7. doi:10.3389/fphar.2016.00130. ISSN 1663-9812.
  11. Kawashima N, Karasawa J, Shimazaki T, Chaki S, Okuyama S, Yasuhara A, Nakazato A (April 2005). "Neuropharmacological profiles of antagonists of group II metabotropic glutamate receptors". Neuroscience Letters. 378 (3): 131–4. doi:10.1016/j.neulet.2004.12.021. PMID 15781145.
  12. Bespalov AY, van Gaalen MM, Sukhotina IA, Wicke K, Mezler M, Schoemaker H, Gross G (September 2008). "Behavioral characterization of the mGlu group II/III receptor antagonist, LY-341495, in animal models of anxiety and depression". European Journal of Pharmacology. 592 (1-3): 96–102. doi:10.1016/j.ejphar.2008.06.089. PMID 18634781.
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  15. Huynh TH, Erichsen MN, Tora AS, Goudet C, Sagot E, Assaf Z, Thomsen C, Brodbeck R, Stensbøl TB, Bjørn-Yoshimoto WE, Nielsen B, Pin JP, Gefflaut T, Bunch L (2016). "New 4-Functionalized Glutamate Analogues Are Selective Agonists at Metabotropic Glutamate Receptor Subtype 2 or Selective Agonists at Metabotropic Glutamate Receptor Group III". J. Med. Chem. 59 (3): 914–24. doi:10.1021/acs.jmedchem.5b01333. PMID 26814576.
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  18. addextherapeutics – ADX71149 for schizophrenia
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  21. EJ Brnardic 2010
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