Cerebrospinal fluid concentrations of N-acetylcysteine after oral administration in Parkinson's disease

Parkinsonism Relat Disord. 2015 May;21(5):500-3. doi: 10.1016/j.parkreldis.2015.02.020. Epub 2015 Feb 28.


Introduction: Depletion of neuronal glutathione may contribute to the pathogenesis of Parkinson's disease (PD). N-acetylcysteine (NAC) can restore neuronal glutathione levels, but it has not been established whether NAC can cross the blood-brain barrier in humans.

Methods: Twelve patients with PD were given oral NAC twice daily for 2 days. Three doses were compared: 7 mg/kg, 35 mg/kg, and 70 mg/kg. NAC, cysteine, and glutathione were measured in the cerebrospinal fluid (CSF) at baseline and 90 min after the last dose. Cognitive and motor functions were assessed pre- and post-NAC administration using the Montreal Cognitive Assessment (MoCA) and the Unified Parkinson's Disease Rating Scale part III motor subscore (UPDRS-III).

Results: Oral NAC produced a dose-dependent increase in CSF NAC concentrations (p < 0.001), with the highest dose producing a CSF concentration of 9.26 ± 1.62 μM. There were no significant adverse events. NAC had no acute effect on motor or cognitive function.

Conclusion: Orally administered NAC produces biologically relevant CSF NAC concentrations at doses that are well tolerated. The findings support the feasibility of NAC as a potential disease-modifying therapy for PD.

Keywords: Cysteine; Glutathione; Neuroprotection; Parkinson's disease; Therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcysteine / administration & dosage*
  • Acetylcysteine / cerebrospinal fluid*
  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Biomarkers / cerebrospinal fluid
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Male
  • Middle Aged
  • Parkinson Disease / cerebrospinal fluid*
  • Parkinson Disease / drug therapy*


  • Biomarkers
  • Acetylcysteine