probenecid + n-acetyl cysteine

Probenecid + n-acetyl cysteine is an investigational combination therapy consisting of two FDA-approved small molecules, probenecid and N-acetylcysteine (NAC), repurposed for neuroprotection in central nervous system (CNS) injuries such as traumatic brain injury (TBI). Probenecid is a classic inhibitor of ATP-binding cassette (ABC) and solute carrier (SLC) membrane transporters, including organic anion transporters OAT1 and OAT3. It blocks the efflux of organic acids like NAC from the brain, thereby increasing their CNS concentrations. NAC acts as a precursor to glutathione synthesis by serving as a cysteine donor, supporting antioxidant defenses. The combination aims to synergistically preserve intracellular glutathione via distinct mechanisms—probenecid prevents glutathione efflux while NAC replenishes its synthesis—potentially reducing neuronal death after injury. This strategy has been evaluated in Phase I clinical trials in children with severe TBI, showing feasibility and safety with detectable CNS drug levels[1][2][3][8].

Other names

probenecid and n-acetylcysteinePro-NAC