Fospropofol Disodium

Fospropofol is a water-soluble prodrug of propofol that has gained increasing attention in the field of anesthesia due to its gentle modulation of cerebral blood flow and metabolism. This review summarizes the pharmacological mechanisms by which fospropofol regulates cerebral hemodynamics, including direct effects on vascular smooth muscle and indirect modulation via suppression of neural metabolic activity. The article also discusses its ability to reduce cerebral metabolic rate, inhibit neuronal excitability, and modulate energy balance, all of which contribute to its potential neuroprotective properties, particularly in ischemia-reperfusion injury. Preclinical and clinical studies suggest that fospropofol exerts antioxidant and anti-inflammatory effects that may further support neural preservation. Clinically, fospropofol has shown value in various scenarios requiring precise neuromanagement, including neurosurgery, anesthesia in elderly patients, intensive care sedation, and perioperative neuroprotection. Despite promising results, further high-quality, large-scale studies are needed to clarify its neuroprotective efficacy across diverse patient populations and surgical contexts. With its favorable pharmacokinetics, controllable depth of sedation, and multitargeted neural effects, fospropofol is poised to become an important tool in individualized neuroanesthesia and brain-protective strategies.

Xanthine dehydrogenase (XDH) contributes significantly to generating reactive oxygen species in coronary artery disease (CAD). XDH has been proposed as a therapeutic target, but its genetic variants could affect protein structure and drug response. We aimed to assess protein structure modification occur due to genetic variants and to screen 215 CAD drugs for their utility in personalized CAD treatment against the XDH variants. A series of computational methods were implemented to identify pathogenic variants that cause XDH structure instability localized at the con served regions contributing to functional significance. Then, the XDH structures with the pathogenic variants were modeled using two different approaches to select the best models for docking with the CAD drugs. Finally, the stability of the docked complexes and their ability to transfer electrons were evaluated using molecular dynamics (MD) simulations and quantum mechanics/molecular mechanics (QM/MM) calculation. Among 751 variants examined; R149C and Q919R showed high pathogenicity, localized in conserved regions could alter protein structure and function. Further, docking of CAD drugs against XDH (native, R149C and Q919R) showed vericiguat with higher affinity, ranging from −7.95 kcal/mol to −10.41 kcal/mol, than the well-known XDH inhibitor (febuxostat, −5.73 kcal/mol to −8.35 kcal/mol). This indicates that vericiguat will be effective in CAD treatment, regardless of the XDH variants. Additionally, MD simulation and QM/MM confirmed vericiguat stability and electron transfer ability to form hydrogen bonds with the XDH protein. In conclusion, vericiguat will be beneficial for the personalized treatment of CAD by inhibiting XDH variants. Additional clinical studies are necessary to confirm our findings.