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]
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mGluR2 Related Products (58)
Related Products (58)
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Decoglurant
0 ImagesSynonyms: RO4995819
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mGluR2 modulator 1
0 ImagesmGluR2 modulator 1 (compound 95) is a potent and BBB-penetrated mGluR2 (metabotropic glutamate receptor-2) positive allosteric modulator, with an EC50 of 0.03 μM. mGluR2 modulator 1 can be used for psychosis research.
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LY3020371 hydrochloride
0 ImagesLY3020371 hydrochloride is a potent, selective metabotropic glutamate 2/3 receptor (mGlu2/3) antagonist with Ki of 5.3 and 2.5 nM, potently blocks cAMP formation with IC50 of 16.2 nM. LY3020371 hydrochloride exerts an antidepressant-like signature in vivo.
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Talaglumetad (hydrochloride)
0 ImagesSynonyms: LY-544344 (hydrochloride)Talaglumetad hydrochloride (LY-544344 hydrochloride) is an orally active prodrug of Eglumegad (HY-18941) and a metabotropic glutamate receptor 2/3 (mGluR2/3) agonist. Talaglumetad hydrochloride 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 hydrochloride can be used in research related to metabotropic glutamate receptor 2-associated neurological systems.
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mGluR2 antagonist 1
0 ImagesmGluR2 antagonist 1 is a highly potent, orally bioavailable and selective class of mGluR2 negative allosteric modulator (IC50 of 9 nM) with excellent brain permeability.
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JNJ-42153605
0 ImagesJNJ-42153605 is a positive allosteric modulator of the metabotropic glutamate 2 (mGlu2) receptor with an EC50 of 17 nM.
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TASP0433864
0 ImagesTASP0433864 is a selective positive allosteric modulator (PAM) of metabotropic glutamate 2 (mGlu2) receptor with EC50 values of 199 nM and 206 nM against human and rat mGlu2 receptors, respectively. TASP0433864 has antipsychotic activity.
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Oxomemazine
0 ImagesOxomemazine is a phenothiazine-based histamine H1-receptor blocker. Oxomemazine is a selective antagonist for muscarinic M1 receptor, displays about 20-fold difference in the affinity for high (Ki = 84 nM, M1 receptor) and low (Ki = 1.65 μM, M2 receptor) affinity sites. Oxomemazine is an antihistamine and anticholinergic agent used for the study of cough treatment. Oxomemazine is protective against anaphylactic microshock in guinea pigs.
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LY3020371
0 ImagesCat. No.: HY-131289CAS No.: 1377615-75-2LY3020371 is a potent and selective antagonist of glutamate (mGlu) 2/3 receptor, with Kis of 5.26 and 2.50 nM for hmGluR2 and hmGluR3, respectively. LY3020371 can be used for the research of depression.
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EGLU
0 ImagesSynonyms: (2S)-α-Ethylglutamic acid; (2S)-α-EGLUEGLU ((2S)-α-Ethylglutamic acid; (2S)-α-EGLU) is a potent and competitive mGluR-2 receptor antagonist. EGLU interacts with (lS,3S)-ACPD-sensitive site with a Kd value of 66 μM. EGLU is an antidepressant agent.
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LY2812223
0 ImagesLY2812223 is a highly potent, functionally selective mGlu2 receptor agonist with mGlu2 binding affinity for mGlu2 and mGlu3 (Ki=144 nM and 156 nM, respectively).
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LY2979165
0 ImagesLY2979165 is the alanine proagent of 2812223, a selective and potent orthosteric mGlu2 receptor agonist.
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Pomaglumetad methionil
0 ImagesCat. No.: HY-105040CAS No.: 956385-05-0Synonyms: LY2140023 hydratePomaglumetad methionil (LY2140023 hydrate) is an oral methionine prodrug of the potent specific mGlu2/3 receptor agonist LY404039 (HY-50906). Pomaglumetad methionil is well-tolerated and has a distinct safety profile, and can be used for schizophrenia.
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MGS0274
0 ImagesCat. No.: HY-131336CAS No.: 1501974-69-1MGS0274, an ester-based lipophilic proagent of a metabotropic glutamate (mGlu)2 and mGlu3 receptor agonist MGS0008, shows improved oral bioavailability. MGS0274 has the potential for the research of schizophrenia.
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mGluR2 modulator 5
0 ImagesCat. No.: HY-168028CAS No.: 1639898-35-3mGluR2 modulator 5 (Compound 11) is an orally active, selective mGluR2 negative allosteric modulator with an IC50 of 8.9 nM. Pharmacokinetic studies in rats show that mGluR2 modulator 5 can effectively cross the blood-brain barrier. It can modulate cognitive and neurological functions in mood disorders and is suitable for research in the field of neurodegenerative diseases.
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LY3027788
0 ImagesCat. No.: HY-117606CAS No.: 1377615-76-3LY3027788, a diester analog of LY3020371 which is an mGlu2/3 receptor antagonist, is a potent and orally active prodrug of LY3020371. LY3027788 has antidepressant efficacy.
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Ro-65-3479
0 ImagesCat. No.: HY-131292CAS No.: 259134-85-5Ro-65-3479 is a selective metabotropic glutamate receptor (mGlu2/3) antagonist. Ro-65-3479 blocks glutamate-induced signaling and modulates calcium channel activity. Ro-65-3479 is promising for research of disorders involving glutamatergic dysregulation, such as anxiety, schizophrenia, and neurodegenerative diseases.
