Sodium Channel Blocker Development for Stroke

Stroke triggers a vicious cycle of electrical and chemical events, including ischemic depolarization, glutamate release, and changes in calcium homeostasis. Current neuroprotective strategies focus on interfering with one or more of these processes. However, N-methyl-d-aspartate (NMDA) receptor antagonists have not been successful in phase III clinical trials. As a result, many researchers have focused their attention on alternative targets, such as voltage-gated Na⁺ channels. Voltage-gated Na⁺ channels are thought to play a key role in excitotoxic injury. Na⁺ channel blockers inhibit neuronal depolarization, glutamate release, and inward Na⁺ flow, thereby reducing inward Ca²⁺ flow through reversal of Ca²⁺ channels, NMDA receptor channels, and Na⁺ /Ca²⁺ exchangers.

Fig. 1. The effect of BIII 890 CL on veratridine-induced glutamate release and neurotoxicity in serum-free cultures of rat cortical neurons. (Carter, et al., 2000)

Our Sodium Channel Blocker Development Services

Ace Therapeutics is a leading global provider of stroke drug development services. Our extensive experience and expertise in this field can help clients investigate the role of voltage-gated Na⁺ channels in cerebral ischemia. In addition, we also assist clients in the development of specific high-affinity Na⁺ channel blockers. Our fully equipped laboratories have advanced equipment for molecular biology, cell culture, drug screening, and imaging studies. This allows us to perform complex experiments and generate reliable data to support the development of Na⁺ channel blockers for the treatment of stroke.

Our services cover the entire process of Na⁺ channel blocker discovery and development, from compound design, optimization, in vitro and in vivo testing, to safety assessment. We also provide expert guidance from an experienced consulting and project management team to help you bring your Na⁺ channel blocker to market quickly, safely, and cost-effectively.

Design and Optimization of Sodium Channel Targeting Compounds

We use a variety of techniques, including high-throughput screening, molecular modeling, medicinal chemistry, structural biology, and computational chemistry, to help clients design and optimize stroke drugs that target sodium channels.

• Targeting voltage-gated sodium channel ligands
• Acid-sensing ion channel blockers

Preclinical Evaluation of Sodium Channel Blockers

Ace Therapeutics conducts rigorous preclinical evaluations to test the therapeutic efficacy of sodium channel blockers in in vitro and animal models of stroke. Our deep expertise in pharmacology and toxicology allows us to design and conduct comprehensive studies to measure the potential effects of sodium channel blockers on the central nervous system to ensure a full understanding of the safety of sodium channel blockers.

• In vitro studies. We utilize primary cultures of cortical neurons for excitotoxicity assays to determine the potential neuroprotective effects of sodium channel blockers. Our expert team performs electrophysiological experiments using whole-cell patch clamp technology. By transfecting neuronal cells with wild-type or mutant brain type II sodium channel α-subunits, we can help clients study the effect of the compound under test on sodium channels.
• In vivo studies. We provide animal models of stroke to study the effects of sodium channel blockers on stroke-related outcomes such as infarct volume, neurological deficits, and functional recovery. We can evaluate the efficacy of sodium channel blockers in modulating glutamate release. We use brain slices from animal cortex or striatum to measure glutamate concentrations using high-performance liquid chromatography and fluorescence detection.

Ace Therapeutics provides comprehensive services for the development of Na⁺ channel blockers for the treatment of stroke. By partnering with us, you will benefit from an unparalleled breadth of scientific expertise, strategic insight, and result delivery support. If you are interested in our services, please do not hesitate to contact us!

1. Carter, A. J., et al. (2000). Potent blockade of sodium channels and protection of brain tissue from ischemia by BIII 890 CL. Proceedings of the National Academy of Sciences, 97(9), 4944-4949.