Metabotropic Glutamate Receptor (mGluR) Antagonist Development for Stroke

Glutamate-mediated excitotoxicity is the most studied mechanism in the pathophysiology of ischemic stroke. Glutamate binds to two types of receptors on postsynaptic neurons: ionotropic glutamate receptors (NMDARs and AMPARs) and metabotropic glutamate receptors (mGluRs). The mGluRs are classified into eight isoforms and three subgroups based on their homologous sequences and their effects on cellular signaling. The mGluRs provide fine control of glutamate activity by activating independent cellular signaling to stimulate multiple cellular signaling pathways. The diversity and heterogeneous distribution of mGluR isoforms in the brain may allow the targeting of specific mGluR isoforms associated with different functions of the CNS, contributing to the development of novel therapeutic strategies for stroke.

Fig. 1. Inhibition of mGluR5 improves lost sensorimotor function after photothrombotic stroke in rats. (Hakon et al., 2024)

Our mGlu Antagonist Development Services

At Ace Therapeutics, we are at the forefront of providing preclinical stroke drug development services. The extensive experience and expertise in this field of our multidisciplinary team of experts, including biologists, chemists and pharmacologists, can provide reliable design and development of novel stroke drugs targeting mGluRs. Our well-equipped laboratories have advanced equipment for molecular biology, cell culture, drug screening and imaging research. This enables us to perform complex experiments and generate reliable data.

Types of mGlu Antagonists We Can Develop

Combined with high-throughput screening, computational methods, in vitro assays, and animal stroke models, we help clients develop drugs that selectively target different mGluR subtypes associated with stroke.

Targeting group I metabotropic receptors：mGluR1 and mGluR5

Targeting group II metabotropic receptors：mGluR2 and mGluR3

Targeting group III metabotropic receptors：mGluR4, mGluR6, mGluR7, and mGluR8

Preclinical Evaluation of mGlu Antagonists

Ace Therapeutics conducts rigorous preclinical evaluations to test the therapeutic efficacy of stroke drugs targeting mGluRs in animal models of stroke. Our deep expertise in pharmacology and pathology allows us to design and execute comprehensive studies to measure the potential effects of your drugs on the central nervous system to ensure a complete understanding of the drug's safety.

• Behavioral analysis: Foot fault test, grip strength test, rotating rod test
• TTC staining of brain slices
• Histopathology of nasal mucosal toxicity
• Blood-brain barrier (BBB) permeability analysis
• Magnetic resonance imaging (MRI) analysis of cerebral infarct volume
• Resting state functional connectivity and network analysis
• Measurement of inositol polyphosphate hydrolysis

Ace Therapeutics is committed to developing a wide range of stroke drugs that selectively target mGluRs, either through antagonism of group I mGluRs, activation of groups II and III mGluRs, or a mixture of class I antagonism/class II or class III agonism. We provide reliable scientific data and maintain the highest ethical standards throughout the development process. If you are interested in our services, please do not hesitate to contact us!

1. Hakon, J., et al. (2024). Inhibiting metabotropic glutamate receptor 5 after stroke restores brain function and connectivity. Brain, 147(1), 186-200.