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]
-
mGluR5 Related Products (74)
Related Products (74)
-
Antibodies (1)
-
(S)-3,5-DHPG
0 Images(S)-3,5-DHPG is a weak, but selective group I metabotropic glutamate receptors (mGluRs) agonist with Ki values of 0.9 μM and 3.9 μM for mGluR1a and mGluR5a, respectively. (S)-3,5-DHPG exhibits anxiolytic activity in rats subjected to hypoxia.
-
SIB-1757
0 ImagesSIB-1757 is a highly selective and noncompetitive antagonist of mGlu5 receptor with an IC50 of 0.4 μM.
-
VU0360172
0 ImagesVU0360172 is a potent and selective mGlu5 receptor positive allosteric modulator with an EC50 value of 16 nM and a Ki of 195 nM, respectively. VU0360172 stimulates polyphosphoinositide (PI) hydrolysis in vivo, which is abrogated in mGlu5 receptors gene deleted mice. VU0360172 is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
-
Zabaglurant
0 ImagesSynonyms: HTL0014242; HTL14242HTL14242 (HTL0014242) is an advanced and orally active mGlu5 NAM with a pKi and a pIC50 of 9.3 and 9.2, respectively. HTL14242 can be used for the research of parkinson’s disease.
-
Dipraglurant
0 ImagesSynonyms: ADX48621Dipraglurant (ADX48621) is a potent, selective, orally active and brain penetrant mGluR5 negative allosteric modulator (NAM), with an IC50 of 21 nM. Dipraglurant can reduce Levodopa-induced dyskinesia (LID) in vivo. Dipraglurant is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
-
DCG-IV
0 ImagesDCG-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.
-
FTIDC
0 ImagesFTIDC is an orally active, noncompetitive, selective allosteric metabotropic glutamate receptor (mGluR) 1 antagonist with an IC50 of 5.8 nM for human mGluR1a. FTIDC has no species differences in its antagonistic activity on recombinant human, mouse, and rat mGluR1.
-
VU0364770
0 ImagesVU0364770 is a selective and potent positive allosteric modulator (PAM) of mGlu4. VU0346770 exhibits EC50s of 290 nM and 1.1 μM at rat mGlu4 and human mGlu4 receptor, respectively. VU0364770 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 also possesses activity at MAO with Ki values of 8.5 and 0.72 μM for human MAO-A and human MAO-B, respectively.
-
VU6043653
0 ImagesVU6043653 is a potent, selective and cross the blood-brain barrier metabotropic glutamate receptor subtype 5 (mGlu5) negative allosteric modulator with an IC50 value of 325 nM for h mGlu5.
-
AZD6538
0 ImagesCat. No.: HY-119282CAS No.: 453566-30-8AZD6538 is a potent, selective and brain penetrant mGluR5 negative allosteric modulator. AZD6538 inhibits DHPG (HY-12598A)-stimulated intracellular Ca2+ release in HEK cells expressing rat or human mGluR5, with IC50 values of 3.2 and 13.4 nM for rat mGluR5 and human mGluR5, respectively. AZD6538 can be used for the research of neuropathic pain.
-
Auglurant
0 ImagesSynonyms: VU0424238Auglurant (VU0424238) is a novel and selective mGlu5 antagonist with an IC50 value of 11 nM (rat) and an IC50 value of 14 nM (human). Auglurant (VU0424238) has an acceptable CNS penetration.
-
VU0409106
0 ImagesVU0409106 is a potent and selective mGlu5 negative allosteric modulator (NAM) with an IC50 of 24 nM. VU0409106 shows anxiolytic effects in rat models in a concentration-dependent manner. VU0409106 also penetrates the blood-brain barrier (BBB).
-
MTEP
0 ImagesMTEP is a potent, non-competitive and highly selective mGluR5 antagonist, with an IC50 of 5 nM and a Ki of 16 nM. MTEP shows antidepressant and anxiolytic-like effects. MTEP can be used for Parkinson's disease research. MTEP is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
-
A-841720
0 ImagesA-841720 is a potent, non-competitive and selective mGlu1 receptor antagonist with an IC50 of 10 nM for human mGlu1 receptor. A-841720 displays 34-fold selectivity over mGlu5 (IC50 of 342 nM), and no significant activity at a range of other neurotransmitter receptors, ion channels, and transporters. A-841720 has the potential for chronic pain research.
-
VU0477573
0 ImagesCat. No.: HY-115483CAS No.: 1946021-40-4VU0477573 is a brain-penetrant partial negative allosteric modulator of metabotropic glutamate receptor subtype 5 (mGluR5). VU0477573 exhibits neuroprotective and anxiolytic effects. VU0477573 can be used for the research of neurological disease, such as Parkinson disease.
-
VU0424465
0 ImagesVU0424465 is a potent and partial PAM (positive allosteric modulator)-agonist for mGlu5 mediated iCa2+ mobilization. VU0424465 exhibits high affinity at MPEP allosteric binding site, with a Ki value of 11.8 nM. VU0424465 is also a agonist for pERK1/2 in cortical neurons.
-
BMT-145027
0 ImagesCat. No.: HY-100728CAS No.: 2018282-44-3BMT-145027 is an mGluR5 positive allosteric modulator without inherent agonist activity, exhibits an EC50 of 47 nM.
