ar-9281 has been researched along with Neuralgia* in 2 studies
2 other study(ies) available for ar-9281 and Neuralgia
| Article | Year |
|---|---|
Movement to the Clinic of Soluble Epoxide Hydrolase Inhibitor EC5026 as an Analgesic for Neuropathic Pain and for Use as a Nonaddictive Opioid Alternative.
This report describes the development of an orally active analgesic that resolves inflammation and neuropathic pain without the addictive potential of opioids. EC5026 acts on the cytochrome P450 branch of the arachidonate cascade to stabilize epoxides of polyunsaturated fatty acids (EpFA), which are natural mediators that reduce pain, resolve inflammation, and maintain normal blood pressure. EC5026 is a slow-tight binding transition-state mimic that inhibits the soluble epoxide hydrolase (sEH) at picomolar concentrations. The sEH rapidly degrades EpFA; thus, inhibiting sEH increases EpFA Topics: Analgesics; Animals; Clinical Trials, Phase I as Topic; Dogs; Endoplasmic Reticulum Stress; Enzyme Inhibitors; Epoxide Hydrolases; Horses; Humans; Inflammation; Male; Molecular Structure; Neuralgia; Phenylurea Compounds; Rats, Sprague-Dawley; Structure-Activity Relationship | 2021 |
Optimized inhibitors of soluble epoxide hydrolase improve in vitro target residence time and in vivo efficacy.
Diabetes is affecting the life of millions of people. A large proportion of diabetic patients suffer from severe complications such as neuropathic pain, and current treatments for these complications have deleterious side effects. Thus, alternate therapeutic strategies are needed. Recently, the elevation of epoxy-fatty acids through inhibition of soluble epoxide hydrolase (sEH) was shown to reduce diabetic neuropathic pain in rodents. In this report, we describe a series of newly synthesized sEH inhibitors with at least 5-fold higher potency and doubled residence time inside both the human and rodent sEH enzyme than previously reported inhibitors. These inhibitors also have better physical properties and optimized pharmacokinetic profiles. The optimized inhibitor selected from this new series displayed improved efficacy of almost 10-fold in relieving pain perception in diabetic neuropathic rats as compared to the approved drug, gabapentin, and previously published sEH inhibitors. Therefore, these new sEH inhibitors could be an attractive alternative to treat diabetic neuropathy in humans. Topics: Administration, Oral; Amines; Analgesics; Animals; Biological Availability; Chemistry Techniques, Synthetic; Crystallography, X-Ray; Cyclohexanecarboxylic Acids; Diabetes Mellitus, Type 1; Diabetic Neuropathies; Drug Design; Enzyme Inhibitors; Epoxide Hydrolases; Gabapentin; gamma-Aminobutyric Acid; Humans; Male; Mice; Molecular Targeted Therapy; Neuralgia; Rats, Sprague-Dawley; Solubility; Structure-Activity Relationship; Time Factors | 2014 |