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Comment · Tue, January 13, 2015 · Ceretropic

Very confused about NAC.. Is it pro-glutamanergic or anti-glutamanergic? Pro-dopaminergic or anti-dopaminergic? All I see is 'modulates glutamate and dopamine' which isn't much help

Original post in this thread

Mushubeans · 24 points

Either way, too high a dose makes me feel depressed but I want to know what exactly it's doing.

What they were answering

cobue · 3 points

What effect do glutamate modulators have?

u/MisterYouAreSoDumb · Ceretropic

Basically NAC tricks the body into releasing less glutamate. So it is not blocking the effects of extracellular glutamate at the post-synaptic receptors, like a traditional antagonist. It is metabolizing to cysteine, which binds to the glutamate-cystine antiporter. The glutamate-cystine antiporter is a plasma membrane transporter that exchanges glutamate for cysteine. This binding reverses the pre-synaptic glutamate transporter, releasing glutamate into the extracellular space, causing the inhibitory metabotropic glutamate receptors to tell the brain to release less glutamate in response. Also, the uptake of cysteine into the cell increases the synthesis of glutathione, which is your body's primary antioxidant.

So essentially it increases the uptake of cysteine into the cell through the glutamate-cystine antiporter, reversing the antiporter, which leads to increased amounts of glutamate binding to the inhibitory metabotropic glutamate receptors. That tells your brain that there is too much glutamate, causing it to slow the release in other areas of the brain. At the same time, that increased cellular cysteine causes an increase in the production of glutathione, protecting your cells from oxidative compounds.

More NAC = more cysteine = more glutamate pre-synaptically = less glutamate release + more antioxidant action

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