mGluR2

Metabotropic glutamate receptor 2 (mGluR2) functions as a presynaptic inhibitory receptor regulating glutamatergic neurotransmission through Galpha inhibitory subunits^[1]. Mechanistically, mGluR2 modulates synaptic plasticity at hippocampal mossy fiber-CA3 synapses, mediating transient suppression of transmission, long-term depression (LTD), and inhibition of long-term potentiation (LTP)^[1]. Compared with its closely related isoform mGluR3, mGluR2 exhibits distinct presynaptic localization and does not directly promote neural progenitor proliferation via ERK1/2 or JNK2 signaling^[2]. In disease models, mGluR2 contributes to fear extinction in the lateral amygdala through long-term weakening of presynaptic release probability^[3], while peripheral mGluR2 activation reduces prostaglandin E2-induced nociceptive sensitization^[4]. In COVID-19 patients, anti-mGluR2 autoantibodies have been identified, indicating immune system cross-reactivity and potential neurological implications^[5]. Pharmacologically, mGluR2-selective agonists, such as LY395756, modulate NMDA receptor expression and function, whereas positive allosteric modulators like (+)-TFMPIP selectively attenuate stress-induced phasic glutamate release without affecting tonic levels^[6]^[7]. These findings highlight mGluR2 as a target for studies of synaptic plasticity, neuropsychiatric disorders, inflammatory pain, and allosteric modulation in experimental models.

References:

[1]. Nicholls RE, et al. mGluR2 acts through inhibitory Galpha subunits to regulate transmission and long-term plasticity at hippocampal mossy fiber-CA3 synapses. Proc Natl Acad Sci U S A. 2006 Apr 18;103(16):6380-5. [Content Brief]

[2]. Wu Z, et al. Identifying Neurological Autoantibodies in COVID-19: mGluR2 as a Marker of Immune Dysregulation During the Omicron Outbreak in China. J Med Virol. 2025 May;97(5):e70381. [Content Brief]

[3]. Guo J, et al. mGluR3 promotes proliferation of human embryonic cortical neural progenitor cells by activating ERK1/2 and JNK2 signaling pathway in vitro. Cell Mol Biol (Noisy-le-grand). 2014;60(2):42-49.

[4]. Yang D, et al. Peripheral group II metabotropic glutamate receptors (mGluR2/3) regulate prostaglandin E2-mediated sensitization of capsaicin responses and thermal nociception. J Neurosci. 2002 Aug 1;22(15):6388-93. [Content Brief]

[5]. Li ML, et al. LY395756, an mGluR2 agonist and mGluR3 antagonist, enhances NMDA receptor expression and function in the normal adult rat prefrontal cortex, but fails to improve working memory and reverse MK801-induced working memory impairment. Exp Neurol. 2015 Nov;273:190-201. [Content Brief]

[6]. Hascup ER, et al. An allosteric modulator of metabotropic glutamate receptors (mGluR₂), (+)-TFMPIP, inhibits restraint stress-induced phasic glutamate release in rat prefrontal cortex. J Neurochem. 2012 Aug;122(3):619-27. [Content Brief]

[7]. Kim J, et al. mGluR2/3 in the Lateral Amygdala is Required for Fear Extinction: Cortical Input Synapses onto the Lateral Amygdala as a Target Site of the mGluR2/3 Action. Neuropsychopharmacology. 2015 Dec;40(13):2916-28. [Content Brief]

mGluR2 Related Products (56):

By Type:	Pan (25) Selective (23)
By Effects:	Inhibitors (4) Agonists (27) Antagonists (14) Activators (2) Modulators (8)

Cat. No.	Product Name	Effect	Purity

HY-W014666

Xanthurenic acid	Agonist	99.53%
Xanthurenic acid is a putative endogenous Group II metabotropic glutamate receptor agonist, on sensory transmission in the thalamus.

HY-70059

LY341495	Antagonist	99.96%
LY341495 is a metabotropic glutamate receptor (mGluR) antagonist with IC₅₀s of 21 nM, 14 nM, 7.8 μM, 8.2 μM, 170 nM, 990 nM, 22 μM for mGlu2, mGlu3, mGlu1a, mGlu5a, mGlu8, mGlu7, and mGlu4 receptors, respectively.

HY-103558

LY379268	Agonist	99.84%
LY379268 is a potent, selective and brain-penetrant mGlu2/3R agonist with EC₅₀ values of 2.69 nM (mGlu2) and 4.48 nM (mGlu3). LY379268 has no activity on human mGlu 1a, 4a, 5a or 7a receptors. LY379268 has antioxidant and neuroprotective effects.

HY-15129

O-Phospho-L-serine	Modulator	99.90%
O-Phospho-L-serine is the immediate precursor to L-cystein in the serine synthesis pathway, and an agonist at the group III mGluR receptors (mGluR4, mGluR6, mGluR7, and mGluR8); O-Phospho-L-serine also acts as a weak antagonist for mGluR1 and a potent antagonist for mGluR2.

HY-18941

Eglumegad	Agonist	99.94%
Eglumegad (LY354740) is a highly potent and selective group II (mGlu2/3) receptor agonist with IC₅₀s of 5 nM and 24 nM on transfected human mGlu2 and mGlu3 receptors, respectively.

HY-131286

Talaglumetad	Activator
Talaglumetad (LY-544344) is an orally active prodrug of Eglumegad (HY-18941) and a metabotropic glutamate receptor 2/3 (mGluR2/3) agonist. Talaglumetad undergoes transmembrane transport via the intestinal peptide transporter hPepT1, and is enzymatically hydrolyzed to produce L-alanine and the parent drug Eglumegad after entering the body. Talaglumetad can be used in research related to metabotropic glutamate receptor 2-associated neurological systems.

HY-131288

LY2934747	Agonist
LY2934747 is a selective and blood-brain barrier-permeable dual mGlu2/mGlu3 receptor agonist, with K_i values of 260 nM and 177 nM, and EC₅₀ values of 8.4 nM and 62.4 nM against human receptors, respectively. LY2934747 exhibits antipsychotic and analgesic activities in in vivo animal models. LY2934747 can be used in studies related to psychosis and pain.

HY-119243

LY2794193	Agonist	99.65%
LY2794193 is a highly potent and selective mGlu3 receptor agonist (hmGlu3 K_i=0.927 nM，EC₅₀=0.47 nM; hmGlu2 K_i=412 nM，EC₅₀=47.5 nM).

HY-12597

Quisqualic acid	Activator	98.0%
Quisqualic acid (L-Quisqualic acid), a natural analog of glutamate, is a potent and pan two subsets (iGluR and mGluR) of excitatory amino acid (EAA) agonist with an EC₅₀ of 45 nM and a K_i of 10 nM for mGluR1R. Quisqualic acid is isolated from the fruits of Quisqualis indica.

HY-100804

L-Cysteinesulfinic acid	Agonist	99.96%
L-Cysteinesulfinic acid is a potent agonist at several rat metabotropic glutamate receptors (mGluRs) with pEC₅₀s of 3.92, 4.6, 3.9, 2.7, 4.0, and 3.94 for mGluR1, mGluR5, mGluR2, mGluR4, mGluR6, and mGluR8, respectively.

HY-15748

JNJ-40411813	Agonist	99.85%
JNJ-40411813 (ADX-71149) is a novel positive allosteric modulator of the metabotropic Glutamate 2 receptor (mGlu2R) with EC₅₀ of 147 nM. JNJ-40411813 has orally bioactivity and penetrate the blood-brain barriers. JNJ-40411813 has the potential property of anti-depression.

HY-W017230

L-Cysteinesulfinic acid monohydrate	Agonist	99.81%
L-Cysteinesulfinic acid monohydrate is a potent agonist at several rat metabotropic glutamate receptors (mGluRs) with pEC₅₀s of 3.92, 4.6, 3.9, 2.7, 4.0, and 3.94 for mGluR1, mGluR5, mGluR2, mGluR4, mGluR6, and mGluR8, respectively.

HY-120717

VU6001966	Inhibitor	99.89%
VU6001966 is a brain-penetrant and selective mGlu2 receptor inhibitor. VU6001966 blocks mGlu2 receptor activity, counteracts LY379268 (HY-103558)-mediated blood-brain barrier protection and inflammatory cytokine dampening in microglia under inflammatory conditions. VU6001966 enhances antidepressant effects when combined with Scopolamine (HY-N0296). VU6001966 can be used for the research of major depressive disorder.

HY-107457

AZD-8529	Agonist	98.17%
AZD-8529 is a potent, highly selective and orally bioavailable positive allosteric modulator of mGluR2, with an EC₅₀ of 285 nM, and shows no positive allosteric modulator responses at 20-25 M on the mGluR1, 3, 4, 5, 6, 7, and 8 subtypes.

HY-50906

LY404039	Agonist	98.0%
LY404039 is a potent, selective and orally active mGluR2 and mGluR3 agonist with K_is of 149 nM and 92 nM for recombinant human mGluR2 and mGluR3, respectively. LY404039 shows >100-fold selectivity for mGluR2/3 over other receptors/transproters. LY404039 has antipsychotic and anxiolytic effects.

HY-101335

DCG-IV	Agonist	99.0%
DCG-IV is a potent agonist of group II mGluRs with EC₅₀s of 0.35 and 0.09 μM for mGlu2R and mGlu3R, reapectively. DCG-IV is also a competitive antagonist at group I (IC₅₀: mGlu1R/5R=389/630 μM) and III receptors (IC₅₀: mGlu4R/6R/7R/8R= 22.5/39.6/40.1/32 μM). DCG-IV has anticonvulsive and neuroprotective effects.

HY-120530

JNJ-46281222	Inhibitor	98.77%
JNJ-46281222 is an metabotropic glutamate (mGlu) 2-selective, highly potent PAM (positive allosteric modulator) with nanomolar affinity (K_d = 1.7 nM) and a high modulatory potency (pEC₅₀ = 7.71).

HY-105040C

Pomaglumetad methionil hydrochloride	Agonist	98.0%
Pomaglumetad methionil hydrochloride (LY2140023 hydrochloride) is an orally active, methionine prodrug of the selective mGlu2/3 receptor agonist LY404039. Pomaglumetad methionil hydrochloride has the potential for schizophrenia research.

HY-107457A

AZD-8529 mesylate	Agonist	99.59%
AZD-8529 mesylate is a potent, highly selective and orally bioavailable positive allosteric modulator of mGluR2, with an EC₅₀ of 285 nM, and shows no positive allosteric modulator responses at 20-25 M on the mGluR1, 3, 4, 5, 6, 7, and 8 subtypes.

HY-16766

Decoglurant	Modulator	99.71%
Decoglurant (RO4995819) is a negative allosteric modulator of mGluR2 and mGluR3. Decoglurant is developed as an antidepressant.

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