Development of New Treatments for Neuropathic Pain Based on Imidazodiazepines

Taylor Wilcox, “Development of New Treatments for Neuropathic Pain Based on Imidazodiazepines”
Mentor: Alexander Arnold, Chemistry & Biochemistry

Currently, 7% of the US population has been diagnosed with neuropathic pain (NP). NP is mediated by inflammation of the associated peripheral sensory endings and is commonly associated with diabetic neuropathy, HIV infection, post-herpetic neuralgia and chemotherapy treatment for cancer. Opioids are currently one of the leading NP therapeutic choices, but their use is controversial. Patients often see minimal benefit but high addiction potential from these drugs. Less than one-fourth of patients have experienced significant pain relief with these treatment options. Neuroinflammation is facilitated by activated microglia, the resident CNS macrophages. They have been implicated in many neuro-inflammatory diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis as well as neuropathic pain. Novel imidazodiazepines have been identified that reduce NO production of microglia, a key inflammatory modulator that causes extensive cell damage. These compounds have been used for decades to target and reduce neuronal firing that leads to pain. Additionally, tuning them to be anti-inflammatory presents a very promising, multi-faceted treatment option that could change the way chronic pain is managed. Safe imidazodiazepines have been developed that are capable of reducing intracellular calcium and nitric oxide. Current compounds of interest to decrease painful neuropathic stimuli are GL-IV-03 and MP-IV-010, among many more. We have applied a combined Greiss assay to quantify the amount of produced NO and a cytotoxicity assay that quantifies the amount of intracellular ATP to test hit compounds in a concentration-dependent manner. These imidazodiazepines show potential as new treatments.

Synchronous Presentation April 16th at 1:00pm

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Comments

  1. Hello I am Taylor Wilcox, an undergraduate at UWM studying BioChemistry. I will be presenting my research regarding the development of new treatments for neuropathic pain. During my presentation I will discuss the importance and relevance of my research, the basis of the Griess Assay which quantifies potential hit compounds, as well as share profound compounds which have been discovered thus far. My presentation will begin at 1:00 pm, and I hope to see you there. If there are any questions, I would love to answer them during my live session and well as via email.

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