Fast Analgesic Effect in Response Test with Topical Phenytoin Cream Correlates with Prolonged Pain Relief After Extended Use in Painful Diabetic Neuropathy

Pharmaceuticals, Год журнала: 2025, Номер 18(2), С. 228 - 228

Опубликована: Фев. 7, 2025

Background: Treatment of painful diabetic neuropathy (PDN) poses several challenges due to the limited effectiveness, high incidence side effects, and potential drug interactions oral neuropathic pain medication. Lacking systemic topical phenytoin cream offers a promising innovative approach addressing unmet needs in treatment. In this retrospective study patients with PDN, we evaluated analgesic effect response tests after extended use. Methods: We collected data from PDN who, prior prolonged use 10% or 20% cream, either had an open test (ORET), single-blind (SIBRET), double-blind (DOBRET) placebo-controlled between November 2016 February 2023. A positive ORET was defined as reduction at least two points on 11-point numerical scale (NRS) within 30 min application. SIBRET DOBRET required additional 1 NRS point treated area compared placebo. test, sustained proportion experiencing minimum relief 30% (MPR30: moderate relief) 50% (MPR50: considerable cream. also assessed correlation relief. Results: identified 65 whom 31 (47.7%) test. The median 3.0 (IQR 2.0-4.0). Extended (median 3.3 months, IQR 1.5-12.1]) resulted 4.0 3.0-5.0); 26/31 (83.9%) achieved MPR30, 21/31 (67.7%) MPR50 correlated significantly (τ = 0.72, p < 0.0001). Conclusions: who provided significant

Язык: Английский

Small molecule oxybutynin rescues proliferative capacity of complex III-defective MPCs

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 9, 2024

ABSTRACT Mitochondrial disease encompasses a group of genetically inherited disorders hallmarked by an inability the respiratory chain to produce sufficient ATP. These present with multisystemic pathologies that predominantly impact highly energetic tissues such as skeletal muscle. There is no cure or effective treatment for mitochondrial disease. We have discovered small molecule known oxybutynin can bypass Complex III dysfunction in primary murine and human muscle progenitor cells (MPCs). Oxybutynin administration improves MPC proliferative capacity, enhances cellular glycolytic function, myotube formation. Mechanistically, results from our isothermal shift assay indicates interacts suite proteins involved mRNA processing which then trigger upregulation biological pathways circumvent CIII dysfunction. Taken together, we provide evidence potential therapeutic candidate future

Язык: Английский

Muscarinic acetylcholine type 1 receptor antagonism activates TRPM3 to augment mitochondrial function and drive axonal repair in adult sensory neurons

Molecular Metabolism, Год журнала: 2024, Номер 92, С. 102083 - 102083

Опубликована: Дек. 16, 2024

Язык: Английский