Comment · Wed, November 4, 2020 · ND Owner
Fasoracetam and GABA-B receptors recovery
Original post in this thread
3ric843 · 19 points
Hello everyone,
I see that fasoracetam is marketed as a solution to help your gaba-B receptors recover by up-regulating them. Apparently it helps with withdrawal and lowers tolerance quickly, and repairs you GABA-B receptors.
This sound very interesting to someone like me, who abused gabaergics (phenibut, GHB and alcohol mainly, but also etizolam has been sometimes taken every night for sleep for some periods) in the past and is trying to recover.
But I also read that the up-regulation only lasts while you are supplementing, and there is a rebound when you stop, similar to the one GHB or phenibut does.
So my question is, anyone know if it is just a marketing gimmick?
From my understand, it's either:
1- A healthy person takes it, GABA-B up-regulates, after cessation everything comes back to normal
2- A person with damaged / downregulated GABA-B receptors takes it for a while, it fixes and upregulates its GABA-B receptors, after cessation there is some loss of up-regulation but it stays better than before the fasoracetam cycle
3- A person with damaged / downregulated GABA-B receptors takes it for a while, it upregulates his receptor, but after cessation, everything goes back…
What they were answering
Direct reply to the original post — see the thread post above.
u/MisterYouAreSoDumb · ND Owner
I know a lot of people say fasoracetam is a GABAb antagonist, but that's actually not true. It's actions are much more complex than that. Essentially Fasoracetam modulates the metabotropic glutamate receptors (mGluRs). The mGluRs are not ionotropic receptors like NMDA/AMPA, and do not directly control ion channels like other glutamate receptors. They are actually receptors that modulate downstream signal cascades, and affect other receptors and systems. This means they are not like activating ion receptors, and are not directly controlling influx of calcium/sodium/potassium into cells. They are modulating the excitability/expression of other receptors and ion channels, and affecting pre/postsynaptic responses.
https://www.sciencedirect.com/science/article/abs/pii/S0006899397000644
This is how it affects GABAb receptors. GABA receptors are actually negatively coupled to adenylate cyclase via PTX-sensitive G-proteins. Fasoracetam modulates adenylate cyclase, which consequently goes on to affect expression of GABAb. It is NOT directly binding to GABAb, and is not a GABAb antagonist like many state. It's the modulation of adenylate cyclase that causes that downstream effect. Many people forget that your receptor systems are all linked together in the body/brain. You can affect expression of one without actually directly binding to it. Also, you have different receptors expressed on the same neurons, like GABA and glutamate, which affect each other a lot. Tolerance is a very complex thing that is mediated by many different systems in the body. You have the obvious ones, like GABAb down-regulation, but you also have others like immediate early gene expression changes and desensitization of the receptors themselves. Take nicotine for example. You would think that nicotine down-regulates nicotinic ACh receptors, but it actually up-regulates them. It just also desensitizes them in the process. So the story behind tolerance to GABA compounds is also more complex than initially meets the eye.