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Comment · Mon, November 16, 2020 · ND Owner

What is the role of pyroglutamic acid in the alcohol defense formula?

Original post in this thread

Bierak · 5 points

One of the problems that I have developed over time when I drink alcohol is that it increases the frequency and ease of developing "blackouts", added to that the rebound effect of anxiety has also increased over time. When I was younger, I didn't get those blackout effects.

I wonder if pyroglumatic acid is included in the formula to prevent the harmful effects of alcohol on the NMDA receptor. As I know alcohol works by activating GABA receptors and by blocking NMDA receptors, it is the combination of both that produces the rebound anxiety and the blackouts. The main problem with alcohol for me right now are the blackouts. I also drink less amount and less frequently than when I was young but as you can know it is difficult to not drink when you socialize

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Direct reply to the original post — see the thread post above.

u/MisterYouAreSoDumb · ND Owner

Everyone knows that alcohol binds to the GABA receptors. However, many people don't discuss its NMDA affinities.

Ethanol Inhibits NMDA-Activated Ion Current in Hippocampal Neurons

Ethanol-induced inhibition of NMDA receptor channels

NMDA receptor-mediated synaptic excitation selectively inhibited by ethanol in hippocampal slice from adult rat

So some of alcohol's deleterious effects on cognition are due to its blockage of the NMDA receptors. Pyroglutamic acid is a compound that normalizes the cognitive disruptions from NMDA antagonists.

Oxiracetam and d-pyroglutamic acid antagonize a disruption of passive avoidance behaviour induced by the N-methyl-d-aspartate receptor antagonist 2-amino-5-phosphonovalerate

Thus, by antagonizing alcohol's depressive effect on glutamate, pyroglutamic acid can help with the "sobering" effect. The interesting thing is that pyroglutamic acid also protects from glutamate-induced seizures. So it has a modulating effect.

Protection by pyroglutamic acid and some of its newly synthesized derivatives against glutamate-induced seizures in mice

If you look at the structure of pyroglutamic acid and compare it to the structure of most the racetams, you can see why it might be having this effect. Pyroglutamic acid is very similar to the 2-pyrrolidone structure that all racetams share. It also seems to have a protective effect against osmotic stress, which is an issue with alcohol consumption, too.

Pyroglutamic acid: Throwing light on a lightly studied metabolite

So you were right, pyroglutamic acid was included in the formula to protect against alcohol's effects on the NMDA receptor, and provide a sobering up effect, while also protecting from osmotic stress.

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