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 (73)
-
Antibodies (1)
-
DHPG
0 ImagesSynonyms: (RS)-3,5-DHPGDHPG is the agonist for mGluR 1/5 (EC50 for mGluR 1 is 60 nM) that activates the phospholipase C (PLC) pathway, and leads ultimately to the activation of protein kinase C (PKC).
-
MPEP
0 ImagesMPEP is a potent, selective, noncompetitive, orally active and systemically active mGlu5 receptor antagonist, with an IC50 of 36 nM for completely inhibiting quisqualate-stimulated phosphoinositide (PI) hydrolysis. MPEP has anxiolytic-or antidepressant-like effects. MPEP is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
-
MTEP hydrochloride
0 ImagesMTEP hydrochloride is a potent, non-competitive and highly selective mGluR5 antagonist, with an IC50 of 5 nM and a Ki of 16 nM. MTEP hydrochloride shows antidepressant and anxiolytic-like effects. MTEP hydrochloride can be used for Parkinson's disease research.
-
MPEP Hydrochloride
0 ImagesMPEP Hydrochloride is a potent, selective, noncompetitive, orally active and systemically active mGlu5 receptor antagonist, with an IC50 of 36 nM for completely inhibiting quisqualate-stimulated phosphoinositide (PI) hydrolysis. MPEP Hydrochloride has anxiolytic-or antidepressant-like effects. MPEP (Hydrochloride) is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
-
CTEP
0 ImagesSynonyms: RO 4956371; mGluR5 inhibitorCTEP (RO 4956371) is a novel, long-acting, orally bioavailable allosteric antagonist of mGlu5 receptor with IC50 of 2.2 nM, and shows > 1000-fold selectivity over other mGlu receptors. CTEP is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
-
Basimglurant
0 ImagesSynonyms: RG7090; RO4917523Basimglurant (RG7090; RO4917523) is a selective, orally active, blood-brain barrier permeable negative allosteric modulator of metabotropic glutamate receptor 5 (mGluR5), with a Ki of 1.4 nM (against [3H]-ABP688 (HY-110141)) and 35.6 nM (against [3H]-MPEP (HY-14609A)). Basimglurant inhibits mGlu5-mediated signaling pathways and receptor constitutive activity, regulates dopamine levels in the nucleus accumbens, exerts anxiolytic, antidepressant-like, analgesic and arousal-promoting effects, and alters δ-wave power during non-rapid eye movement sleep. Basimglurant can be used in research on depression, fragile X syndrome, anxiety disorders, etc.
-
Mavoglurant
0 ImagesSynonyms: AFQ056Mavoglurant (AFQ056) is a potent, selective, non-competitive and orally active mGluR5 antagonist, with an IC50 of 30 nM. Mavoglurant shows a >300 fold selectivity for the mGluR5 over all targets (238) tested. Mavoglurant can be used for the research of Fragile X syndrome (FXS), and L-dopa induced dyskinesias in Parkinson's disease. Mavoglurant is a click chemistry reagent, it contains an Alkyne group and can undergo copper-catalyzed azide-alkyne cycloaddition (CuAAc) with molecules containing Azide groups.
-
Nefiracetam
0 ImagesSynonyms: DM9384; DZL-221Nefiracetam is a cognition-enhancing agent. Nefiracetam is an activator of nAChR, N-methyl-D-aspartate receptor (NMDAR), mGluR5, PKC, gamma-aminobutyric acid (GABA), and N/L-type Ca2+ channels. Nefiracetam promotes neuroplasticity and enhances neuroprotection. Nefiracetam can be used in Alzheimer's disease, epilepsy, and cerebral ischemia research.
-
Fenobam
0 ImagesFenobam is a selective and orally active mGluR5 antagonist (IC50=84 nM) that can penetrate the blood-brain barrier. Fenobam shows the Kd values of 54 nM and 31 nM on rat and human recombinant mGlu5 receptors, respectively. Fenobam has anxiolytic activity, inhibits self-administration behavior in mice, and induces apoptosis in cancer cells. Fenobam can be used for research on neurological diseases, cancer and drug addiction.
-
NPS 2390
0 ImagesNPS 2390 is an allosteric antagonist of calcium-sensing receptor (CaSR) and mGluR1/5. NPS 2390 inhibits the PI3K/Akt/mTOR signaling pathway, reduces hypoxia-induced intracellular calcium elevation, decreases the expression of autophagy (autophagy) proteins, regulates the expression of phenotypic marker proteins, and inhibits the proliferation of pulmonary artery smooth muscle cells. NPS 2390 attenuates the endogenous apoptosis (apoptosis) pathway, increases the expression level of Bcl-2, downregulates the expression levels of Bax, cytochrome c and caspase-3, alleviates cerebral edema and improves neurological function in rat models. NPS 2390 can be used in studies related to hypoxic pulmonary hypertension, traumatic brain injury, stroke and pain.
-
JNJ-46778212
0 ImagesSynonyms: VU 0409551JNJ-46778212 (VU 0409551) is an mGlu5 positive allosteric modulator with an EC50 of 260 nM.
-
(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.
