mGluR1

The metabotropic glutamate receptor subtype 1 (mGluR1) is a G-protein coupled receptor that mediates excitatory neurotransmission by activating phospholipase C and subsequent intracellular Ca²⁺ signaling^[1]^[2]. Mechanistically, mGluR1 primarily couples to the Gq/11 family, leading to inositol trisphosphate (IP₃)-dependent Ca²⁺ release and modulation of postsynaptic excitability^[3]^[4]. In cerebellar Purkinje cells, mGluR1a, the predominant isoform, localizes perisynaptically and facilitates long-term depression (LTD) and climbing fiber synapse elimination, whereas the shorter mGluR1b lacks the extended C-terminal domain, resulting in dispersed subcellular distribution and altered IP₃R-mediated Ca²⁺ signaling^[5]^[6]. Compared with mGluR5, mGluR1 exhibits distinct pharmacology, including selective sensitivity to non-competitive antagonists like cyclothiazide and agonist potency dependent on the C-terminal domain^[7]^[8]. In experimental disease models, mGluR1 expression is dynamically regulated in neurodegeneration and stress paradigms, contributing to synaptic plasticity deficits, excitotoxicity, and hippocampal signaling alterations^[9]^[10]. Agonists and allosteric modulators of mGluR1 have been utilized to investigate synaptic transmission, motor coordination, and learning in rodent models, with subtype-selective agents enabling differentiation from mGluR5-mediated effects^[11]^[12]. These characteristics make mGluR1 a critical target for dissecting group I mGluR function, understanding isoform-specific signaling, and designing pharmacological interventions in central nervous system studies^[1]^[2]^[5]^[7].

References:

[1]. Ohtani Y, et al. The synaptic targeting of mGluR1 by its carboxyl-terminal domain is crucial for cerebellar function. J Neurosci. 2014 Feb 12;34(7):2702-12.

[2]. Flor PJ, et al. The C-terminal domain of the mGluR1 metabotropic glutamate receptor affects sensitivity to agonists. J Neurochem. 1996 Jul;67(1):58-63.

[3]. Kumpost J, et al. Surface expression of metabotropic glutamate receptor variants mGluR1a and mGluR1b in transfected HEK293 cells. Neuropharmacology. 2008 Sep;55(4):409-18.

[4]. Sun YG, et al. mGluR1 and mGluR5 Synergistically Control Cholinergic Synaptic Transmission in the Thalamic Reticular Nucleus. J Neurosci. 2016 Jul 27;36(30):7886-96.

[5]. Surin A, et al. Cyclothiazide selectively inhibits mGluR1 receptors interacting with a common allosteric site for non-competitive antagonists. Neuropharmacology. 2007 Mar;52(3):744-54.

[6]. Mary S, et al. A cluster of basic residues in the carboxyl-terminal tail of the short metabotropic glutamate receptor 1 variants impairs their coupling to phospholipase C. J Biol Chem. 1998 Jan 2;273(1):425-32.

[7]. Dyka FM, et al. Metabotropic glutamate receptors are differentially regulated under elevated intraocular pressure. J Neurochem. 2004 Jul;90(1):190-202.

[8]. Wierońska JM, et al. Olfactory bulbectomy and amitriptyline treatment influences mGlu receptors expression in the mouse brain hippocampus. Pharmacol Rep. 2008 Nov-Dec;60(6):844-55.

[9]. Gereau RW 4th, et al. Multiple presynaptic metabotropic glutamate receptors modulate excitatory and inhibitory synaptic transmission in hippocampal area CA1. J Neurosci. 1995 Oct;15(10):6879-89.

[10]. 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]

mGluR1 Related Products (47):

By Type:	Pan (12) Selective (21)
By Effects:	Inhibitors (3) Agonists (10) Antagonists (26) Activators (3) Modulators (5)

Cat. No.	Product Name	Effect	Purity

HY-100403

Ro 67-7476	Agonist	99.69%
Ro 67-7476 is a potent positive allosteric modulator of mGluR₁ and potentiates glutamate-induced calcium release in HEK293 cells expressing rat mGluR1a with an EC₅₀ of 60.1 nM. Ro 67-7476 is a potent P-ERK1/2 agonist and activates ERK1/2 phosphorylation in the absence of exogenously added glutamate (EC₅₀=163.3 nM).

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-12598A

DHPG	Agonist	99.60%
DHPG 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).

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-100407

JNJ16259685	Antagonist	99.94%
JNJ16259685 is a selective antagonist of mGlu1 receptor, and inhibits the synaptic activation of mGlu1 in a concentration-dependent manner with IC₅₀ of 19 nM.

HY-103566A

LY456236 free base	Antagonist
LY456236 free base is a selective, non-competitive and orally active antagonist of glutamate receptor 1 (mGlu1), which can inhibit phosphatidylinositol hydrolysis with an IC₅₀ of 0.145 μM. LY456236 free base can also inhibit EGFR, with an IC₅₀ of 0.918 μM. LY456236 free base blocks cell proliferation by inhibiting the MAPK pathway, reversing the anti-apoptotic effect of DHPG (HY-12598A). LY456236 free base can be used in epilepsy research.

HY-114891

R214127	Antagonist
R214127 is a selective mGlu1 receptor antagonist with IC₅₀ values of 6 and 14 nM for rat and human mGlu1a. R214127 acts on a site from the glutamate binding pocket, and competes for the same transmembrane segment VII as other noncompetitive mGlu1 antagonists.

HY-175100

HexylHIBO hydrobromide	Antagonist
HexylHIBO hydrobromide is a potent group I mGluR antagonist with Kbs of 140 μM and 110 μM at mGlu_1a and mGlu_5a receptors, respectively. HexylHIBO hydrobromide does not inhibits mGlu2 and mGlu4a. HexylHIBO hydrobromide decreases spontaneous excitatory postsynaptic currents (sEPSCs) in rat.

HY-100786

DL-AP3	Antagonist	≥98.0%
DL-AP3 is a competitive mGluR1 and mGluR5 antagonist. DL-AP3 is also an inhibitor of phosphoserine phosphatase. DL-AP3 has neuroprotective effect.

HY-107515A

LY367385 hydrochloride	Antagonist	99.44%
LY367385 hydrochloride is a highly selective and potent mGluR1a antagonist. LY367385 hydrochloride has an IC₅₀ of 8.8 μM for inhibiting of quisqualate-induced phosphoinositide (PI) hydrolysis, compared with >100 μM for mGlu5a. LY367385 hydrochloride has neuroprotective, anticonvulsant and antiepileptic effects.

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-100605

VU0483605	Modulator
VU0483605 is a potent and brain-penetrated mGlu₁ receptor positive allosteric modulator (PAM). VU0483605 shows excellent mGlu₁ PAM activity at both human and rat, with EC₅₀ values of 390 and 356 nM, respectively.

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-11095

NPS 2390	Antagonist	99.90%
NPS 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.

HY-101356

CPCCOEt	Antagonist	98.31%
CPCCOEt is a low affinity, selective, non-competitive and reversible antagonist of metabotropic glutamate receptor 1b (mGluR1b).

HY-100382

FPTQ	Antagonist	99.92%
FPTQ is potent mGluR₁ antagonist with IC₅₀ values of 6 nM and 1.4 nM for human and mouse mGluR1 respectively. FPTQ has anti-oxidant and anti-inflammatory effects in vitro and in vivo.

HY-12598

(S)-3,5-DHPG	Agonist	99.82%
(S)-3,5-DHPG is a weak, but selective group I metabotropic glutamate receptors (mGluRs) agonist with K_i 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.

HY-101845

FITM	Inhibitor	98.00%
FITM is a negative allosteric modulator of mGlu1 receptor with a K_i of 2.5 nM.

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.

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