Excitotoxicity Inhibitor Development
An excitotoxicity inhibitor is a substance or compound which blocks or limits the harmful effect of excitotoxicity. Because of the excitotoxicity mechanism in some rare neurologic disorders, Protheragen has spent considerable effort and advanced technologies assembling a team of specialists concentrating on the excitotoxicity inhibitor development. With our dedicated support services, we help the clients transit seamlessly from the drug development phase to the marketing phase.
Overview of Excitotoxicity Inhibitors
Excitotoxicity is a pathological condition brought about by the excess stimulation of glutamate receptors which results in the damage and death of neurons. This phenomenon is implicated in numerous neurological disorders such as amyotrophic lateral sclerosis (ALS), Parkinson's disease, Alzheimer's disease, and ischemic stroke. Excitotoxicity inhibitors are pharmacological agents that aim to control the level of activation of glutamate receptors in order to maintain the integrity of neurons.
Fig.1 Neuroplastic drugs rescue glutamate homeostasis reverting glutamate-induced excitotoxicity and its consequences. (Nicosia N, et al., 2024)
Mechanisms of Action of Excitotoxicity Inhibitors
Excitotoxicity inhibitors work through various mechanisms to mitigate neuronal harm inflicted by the over-activation of glutamate receptors, mainly by blocking the doorways to ionotropic receptors (NMDA, AMPA, and kainate) to stave off pathological calcium influx, adjusting metabotropic glutamate receptors (mGluRs) to optimize signaling at synapses, reducing the release of glutamate through sodium channel blockade, augmenting the removal of glutamate through excitatory amino acid transporters, lowering oxidative stress harms and apoptotic death by antioxidant and anti-inflammatory effect.
Fig.2 The proposed mechanism of 14,15-EET/sEH inhibition-mediated neuron-astrocyte interaction for neuroprotection against excitotoxic brain injury. (Kuo Y M, et al., 2019)
Development of Excitotoxicity Inhibitors
| Drug Names | Indications | Targets | Mechanism of Action | Phase |
| Memantine | Alzheimer's disease, Huntington's disease | NMDA receptor | Reduces excessive calcium influx. | Approved |
| Riluzole | Amyotrophic lateral sclerosis (ALS) | Sodium channels, glutamate release | Inhibits presynaptic glutamate release and modulates sodium channels. | Approved |
| Perampanel | Epilepsy | AMPA receptor | Suppresses excitatory neurotransmission. | Approved |
| Basimglurant | Fragile X syndrome | mGluR5 | Normalizes synaptic glutamate signaling. | Phase II |
| Topiramate | Epilepsy | AMPA/kainate receptors, sodium channels | Blocks AMPA/kainate receptors and inhibits glutamate release via sodium channel modulation. | Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen focuses on excitotoxicity inhibitor development for rare neurological disorders using advanced disease models and extensive preclinical research to expedite therapeutic development. All of our capabilities span from target identification to drug efficacy and safety studies, enabling partners to advance new neuroprotective therapies to IND enabling studies.
Diverse Development Platforms for Excitotoxicity Inhibitors
Targets of Excitotoxicity Inhibitor Development
Crafted to target a myriad of molecular pathways, our excitotoxicity inhibitors are adept for treating a diverse spectrum of neurological diseases, adeptly meeting the varied R&D requirements of our customers. Centered on innovation and bespoke solutions, we deliver comprehensive services to effectively tackle the intricate challenges linked with these diseases.
- NMDA receptors
- AMPA receptors
- Kainate receptors
- Metabotropic glutamate receptors
- Excitatory amino acid transporters
- Cystine-glutamate antiporter
- Calcium-permeable ion channels
- Calpain proteases
- More
Workflow of Excitotoxicity Inhibitor Development
Target Identification & Validation
Drug Screening and Optimization
In Vitro Characterization
In Vivo Efficacy Testing
Safety Assessment
IND-Enabling Studies
Specializing in preclinical research for excitotoxicity inhibitor development, Protheragen offers comprehensive solutions encompassing pharmacodynamics (PD), pharmacokinetics (PK) and toxicology studies. We meticulously validate and optimize promising drug candidates, paving the way for their successful commercialization. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Nicosia N, Giovenzana M, Misztak P, et al. Glutamate-mediated excitotoxicity in the pathogenesis and treatment of neurodevelopmental and adult mental disorders[J]. International Journal of Molecular Sciences, 2024, 25(12): 6521.
- Kuo Y M, Hsu P C, Hung C C, et al. Soluble epoxide hydrolase inhibition attenuates excitotoxicity involving 14, 15-epoxyeicosatrienoic acid–mediated astrocytic survival and plasticity to preserve glutamate homeostasis[J]. Molecular Neurobiology, 2019, 56: 8451-8474.