Biochemie

Acetylcysteine - N-acetylcysteine (NAC)

• Acetylcysteine is the N-acetyl derivative of the amino acid L-cysteine
• Precursor of the antioxidant glutathione
• Thiol (sulfhydryl) group confers antioxidant effects
• Able to reduce free radicals
• Soluble in water and alcohol
• Practically insoluble in chloroform and ether [1]

• White to white with light yellow cast powder
• PKa of 9.5 at 30 °C [1]

Mechanismus účinku

Glutathion

• Prodrug to L-cysteine
• Precursor to the biologic antioxidant glutathione
• Administration of acetylcysteine replenishes glutathione stores [1]
• Increasing glutathione levels
• Binding with the toxic breakdown products of paracetamol [1]

• Glutathione, along with oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO)
• Bind to the glutamate recognition site of the NMDA and AMPA receptors
• Via their glutamyl moieties
• May be endogenous neuromodulators
• At millimolar concentrations
• Modulate the redox state of the NMDA receptor complex

• Glutathione
• Bind to and activate ionotropic receptors
• Different from any other excitatory amino acid receptor
• May constitute glutathione receptors
• Potentially making it a neurotransmitter [1]

p53 down-regulace

• NAC does not cause cancer
• Counteracts ROS accumulation caused by p53
• Down-regulates p53
• Prevents p53-induced apoptosis and promotes autophagy
• Dose dependent response
• Ability to manipulate cellular apoptosis and autophagy has many therapeutic benefits [1]

L-cysteine

• Precursor to cystine
• Substrate for the cystine-glutamate antiporter on astrocytes
• Increasing glutamate release into the extracellular space
• Acts on mGluR2/3 receptors
• At higher doses of acetylcysteine, mGluR5 [1]

Anti-inflammatory effects

• V.s. inhibiting NF-kappa B
• V.s. modulating cytokine synthesis [1]

Metabolismus

Extensively liver metabolized

• CYP450 minimal

Urine excretion

• 22-30% with
• Half-life of 5.6 hours in adults
• 11 hours in neonates