mGluR5
Metabotropic glutamate receptor 5 (mGluR5) is a Gq-coupled Group I receptor that modulates excitatory synaptic transmission and intracellular calcium signaling in neurons[1][2]. Mechanistically, mGluR5 activation influences synaptic plasticity by regulating long-term potentiation (LTP) and long-term depression (LTD) through protein synthesis-dependent pathways, particularly in hippocampal CA1 neurons[3][4]. Compared with mGluR1, mGluR5 exhibits higher intracellular localization in neurons, favoring postsynaptic compartments and extrasynaptic sites, which affects receptor trafficking and signaling specificity[5][6]. In developmental and adult cerebellar Purkinje cells, mGluR5 can substitute for mGluR1 to restore motor coordination and synapse elimination, indicating functional overlap despite temporal expression differences[2]. In respiratory network neurons, mGluR5 activation modulates TRPC channel-mediated currents, enhancing regularity of inspiratory rhythms, whereas mGluR1 primarily regulates frequency[7]. Disease relevance is highlighted in addiction models, where mGluR5 antagonism reduces ethanol self-administration, and in autoimmune encephalitis, where anti-mGluR5 antibodies are associated with psychiatric symptoms[8][9]. Agonists such as CHPG and DHPG potentiate mGluR5 signaling in experimental systems, while selective antagonists like MPEP and LY344545 inhibit receptor activity, enabling mechanistic studies of synaptic plasticity and behavioral modulation[1][3][10].
References:
- [1]. Kammermeier PJ. The orthosteric agonist 2-chloro-5-hydroxyphenylglycine activates mGluR5 and mGluR1 with similar efficacy and potency. BMC Pharmacol. 2012 May 29;12:6. doi: 10.1186/1471-2210-12-6. PMID: 22642439; PMCID: PMC3416681. et al. The orthosteric agonist 2-chloro-5-hydroxyphenylglycine activates mGluR5 and mGluR1 with similar efficacy and potency. BMC Pharmacol. 2012 May 29;12:6. [Content Brief]
- [2]. Harbers M, et al. mGluR5 Is Substitutable for mGluR1 in Cerebellar Purkinje Cells for Motor Coordination, Developmental Synapse Elimination, and Motor Learning. Cells. 2022 Jun 23;11(13):2004. [Content Brief]
- [3]. Neyman S, et al. Metabotropic glutamate receptor 1 (mGluR1) and 5 (mGluR5) regulate late phases of LTP and LTD in the hippocampal CA1 region in vitro. Eur J Neurosci. 2008 Mar;27(6):1345-52. [Content Brief]
- [4]. Bikbaev A, et al. MGluR5 mediates the interaction between late-LTP, network activity, and learning. PLoS One. 2008 May 14;3(5):e2155. [Content Brief]
- [5]. Muly EC, et al. Distribution of mGluR1alpha and mGluR5 immunolabeling in primate prefrontal cortex. J Comp Neurol. 2003 Dec 22;467(4):521-35. [Content Brief]
- [6]. Hubert GW, et al. Differential subcellular localization of mGluR1a and mGluR5 in the rat and monkey Substantia nigra. J Neurosci. 2001 Mar 15;21(6):1838-47. [Content Brief]
- [7]. Ben-Mabrouk F, et al. Metabotropic glutamate receptors (mGluR5) activate transient receptor potential canonical channels to improve the regularity of the respiratory rhythm generated by the pre-Bötzinger complex in mice. Eur J Neurosci. 2012 Jun;35(11):1725-37. [Content Brief]
- [8]. Hodge CW, et al. The mGluR5 antagonist MPEP selectively inhibits the onset and maintenance of ethanol self-administration in C57BL/6J mice. Psychopharmacology (Berl). 2006 Jan;183(4):429-38. [Content Brief]
- [9]. Liu Y, et al. Anti-mGluR encephalitis: case series and literature review. BMC Neurol. 2026 Jan 24;26(1):150. [Content Brief]
- [10]. Doherty AJ, et al. A novel, competitive mGlu(5) receptor antagonist (LY344545) blocks DHPG-induced potentiation of NMDA responses but not the induction of LTP in rat hippocampal slices. Br J Pharmacol. 2000 Sep;131(2):239-44. [Content Brief]
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mGluR5 Related Products (74)
Related Products (74)
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Antibodies (1)
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ML353
0 ImagesML353 is a selective ligand of mGlu5 silent allosteric modulator (SAM) with an Ki value of 18.2 nM. ML353 improves the affinity of common allosteric sites, 20-fold higher than the previous mGlu5 SAM tool compound 5mpep. ML353 has potential applications in solving the intrinsic activity of SAM in vivo or as a agent blocker. ML353 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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ML254
0 ImagesCat. No.: HY-16654CAS No.: 1428630-86-7ML254 is a potent mGlu5 potentiator, with EC50 and pEC50 of 9.3 nM and 8.03 nM for rat mGlu5, respectively. ML254 can be used for researching schizophrenia. ML254 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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VU0364770 hydrochloride
0 ImagesVU0364770 hydrochloride is a selective and potent positive allosteric modulator (PAM) of mGlu4. VU0346770 hydrochloride exhibits EC50s of 290 nM and 1.1 μM at rat mGlu4 and human mGlu4 receptor, respectively. VU0364770 hydrochloride exhibits antagonist activity at mGlu5 with a potency of 17.9 μM and PAM activity at mGlu6 with a potency of 6.8 μM. VU0364770 hydrochloride also possesses activity at MAO with Ki values of 8.5 and 0.72 μM for human MAO-A and human MAO-B, respectively.
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VU0360172 hydrochloride
0 ImagesVU0360172 hydrochloride is a potent and selective mGlu5 receptor positive allosteric modulator (PAM) with an EC50 value of 16 nM and a Ki of 195 nM, respectively. VU0360172 hydrochloride stimulates polyphosphoinositide (PI) hydrolysis in vivo, which is abrogated in mGlu5 receptors gene deleted mice.
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AZD 2066
0 ImagesAZD-2066 is a selective, orally active and blood-brain barrier-permeating mGluR5 antagonist. AZD 2066 activates the BDNF/trkB signaling pathway. AZD 2066 can be used in the research of neuropathic pain, major depressive disorder and gastroesophageal reflux disease.
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DCB
0 ImagesDCB (3,3′-dichlorobenzaldazine) is an neutral allosteric modulator of themetabotropic glutamate receptor metabotropic glutamate receptor subtype 5 (mGluR5) . DCB blocks the positive allosteric regulation of mGluRs (mGluR5) with the help of 3,3′-difluorobenzaldazine (DFB). DCB shows the negative modulatory effect of 3,3′-dimethoxybenzaldazine (DMeOB).
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AZD 2066 hydrate
0 ImagesCat. No.: HY-110255AAZD-2066 hydrate is a selective, orally active and blood-brain barrier-permeating mGluR5 antagonist. AZD 2066 hydrate activates the BDNF/trkB signaling pathway. AZD 2066 hydrate can be used in the research of neuropathic pain, major depressive disorder and gastroesophageal reflux disease.
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Mavoglurant racemate
0 ImagesSynonyms: AFQ-056 racemateMavoglurant racemate (AFQ-056 racemate) is the racemate of Mavoglurant. Mavoglurant is a novel, non-competitive mGlu5 receptor antagonist. Mavoglurant (racemate) is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
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Methoxy-PEPy
0 ImagesMethoxy-PEPy is a potent and highly selective mGlu5 receptor antagonist with IC50 of 1 nM.
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VU 0357121
0 ImagesVU 0357121 is a positive and highly selective mGlu5R allosteric modulator (PAM) with an EC50 of 33 nM. VU 0357121 is inactive or very weakly antagonizing at other mGlu receptor subtypes.
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VU0652835
0 ImagesCat. No.: HY-119941CAS No.: 1848252-81-2VU0652835 is a metabotropic glutamate receptor subtype 5 (mGlu5) negative allosteric modulator with an IC50 of 81 nM.
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VU0463841
0 ImagesCat. No.: HY-120527CAS No.: 1439095-16-5VU0463841 is a potent, selective and brain-penetrant mGlu5 negative allosteric modulator (NAM) with an IC50 of 13 nM. VU0463841 is ineffective against mGlu1-4 and mGlu7-8. VU0463841 has the potential for the Cocaine addiction research.
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JF-NP-26
0 ImagesCat. No.: HY-131019CAS No.: 2341841-03-8JF-NP-26, an inactive photocaged derivative of raseglurant, is the first caged mGlu5 receptor negative allosteric modulator. Uncaging of JF-NP-26 is elicited with light pulses in the visible spectrum (405 nm). JF-NP-26 induces light-dependent analgesia in models of inflammatory and neuropathic pain in freely behaving animals.
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LSN2814617
0 ImagesCat. No.: HY-118256CAS No.: 1313498-17-7LSN2814617 is an orally active, potent, brain-penetrant, and selective mGlu5 (metabotropic glutamate 5) positive allosteric modulator (PAM), with EC50 values of 52 nM (Human mGlu5) and 42 nM (rat mGlu5). LSN2814617 shows wake-promoting effect. LSN2814617 can be used for schizophrenia research.
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STX107
0 ImagesCat. No.: HY-W565924CAS No.: 935685-90-8STX107 is a metabotropic glutamate 5 (mGlu5) receptor negative allosteric modulator (NAM) with a pKi of 8.32. STX107 inhibits glutamate-induced Ca2+ mobilization, IP1 accumulation, and ERK1/2 phosphorylation. STX107 also inhibits glutamate-induced mGlu5 internalization.
