Glutathione, along with oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO), have been found to bind to the glutamate recognition site of the NMDA and AMPA receptors (via their γ-glutamyl moieties), and may be endogenous neuromodulators. At millimolar concentrations, they may also modulate the redox state of the NMDA receptor complex. In addition, glutathione has been found to bind to and activate ionotropic receptors that are different from any other excitatory amino acid receptor, and which may constitute glutathione receptors, potentially making it a neurotransmitter. As such, since N-acetylcysteine is a prodrug of glutathione, it may modulate all of the aforementioned receptors as well. Glutathione also modulates the NMDA receptor by acting at the redox site.L-cysteine also serves as a precursor to cystine, which in turn serves as a substrate for the cystine-glutamate antiporter on astrocytes; hence there is increasing glutamate release into the extracellular space. This glutamate in turn acts on mGluR2/3 receptors, and at higher doses of acetylcysteine, mGluR5.Acetylcysteine also possesses some anti-inflammatory effects possibly via inhibiting NF-κB and modulating cytokine synthesis. Pharmacokinetics
Acetylcysteine is extensively liver metabolized, CYP450 minimal, urine excretion is 22–30% with a half-life of 5.6 hours in adults and 11 hours in newborns. Chemistry
Acetylcysteine is the N-acetyl derivative of the amino acid L-cysteine, and is a precursor in the formation of the antioxidant glutathione in the body. The thiol (sulfhydryl) group confers antioxidant effects and is able to reduce free radicals.
Research
While many antioxidants have been researched to treat a large number of diseases by reducing the negative effect of oxidative stress, acetylcysteine is one of the few that has yielded promising results, and is currently already approved for the treatment of paracetamol overdose. In mouse mdx models of Duchennes muscular dystrophy, treatment with 1–2% acetylcysteine in drinking water significantly reduces muscle damage and improves strength. It is being studied in conditions such as autism, where cysteine and related sulfur amino acids may be depleted due to multifactorial dysfunction of methylation pathways involved in methionine catabolism. Animal studies have also demonstrated its efficacy in reducing the damage associated with moderate traumatic brain or spinal injury, and also ischaemia-induced brain injury. In particular, it has been demonstrated to reduce neuronal losses and to improve cognitive and neurological outcomes associated with these traumatic events. It has been suggested that acetylcysteine may help people with Samters triad by increasing levels of glutathione allowing faster breakdown of salicylates, although there is no evidence that it is of benefit. Small studies have shown acetylcysteine to be of benefit to people with blepharitis. It has been shown to reduce ocular soreness caused by Sjögrens syndrome. It has been shown that N-acetylcysteine may protect the human cochlea from subclinical hearing loss caused by loud noises such as impulse noise. In animal models, it reduced age-related hearing loss. It has been shown effective in the treatment of Unverricht-Lundborg disease in an open trial in four patients.