
Originally Posted by
krugerr
How comes the sub-lingual administration gives better results? Is it because it is absorbed slowly, rather than digested?
It is actually absorbed faster sublingually and goes directly into the bloodstream in its unaltered form. The problem is that even though the peptide is small enough to be abosrbed through the GI tract, it seems as though some portion of the Noopept still undergoes some kind of modification, so here we go...
IMPORTANT INFORMATION ON THE ADMINISTRATION OF NOOPEPT - MUST READ!!
Alright, so i've experimented with dosing Noopept in 3 different ways:
- Oral administration
- Sublingual administration
- Neublizing/vaporizing it
After plenty of research and trying primarily oral and sublingual administration, i've found that sublingual administration by far produces a greater immediate effect and an overall better effect than oral administration (even though it has been found in clinical testing that oral administration provides 95% or higher absorbtion. I've also tried nebulizing/vaporizing it but haven't done this enough to be able to gauge any effects properly. The problem is like I said, Noopept seems to undergo a few changes due to enzyme activity and also a few things in regards to the liver metabolism. A simple google search will yield quite a bit of information in the form of personal experience as well as commentary by some people who really know their chemistry well.
Noopept is also highly soluble in alcohol, and while sublingual administration of the powder or tablets directly under the tongue works well, many reccomend mixing it into a very small amount of alcohol (yes, hard liquor or something - you don't need much at all) and then let it rest sublingually under the tongue for maximum transport efficiency into the sublingual membranes. I have not yet tried this but I will some time soon and report my findings. One such study has demonstrated that Noopept is absorbed into the blood stream through the GI tract and crosses the blood brain barrier unchanged(1) while another study demonstrated that Noopept ALSO undergoes hepatic metabolism (liver metabolism) into a metabolized form. So, I think we can conclude pretty distinctly that a good portion of Noopept is absorbed right into the bloodstream through the GI tract but a good portion of it is also metabolized in the liver!
Here is what's actually going on from what i've gathered and from my knowledge of biochemistry in my analysis of the Noopept molecule (I actually hadn't examined it very closely until now): Noopept is a modified polypeptide consisting of an ester (Phenylacetyl ester) and 2 amino acids: Glycine and Proline. It is basically the amino acids Glycine and Proline linked together, with an Phenylacetyl group esterified to the Proline. This forms a peptide molecule, but an extremely small one and with the additional modifications of an ester attached to the amino acids, it is a unique one.
I will explain this better, as usual, with my photoshopped pictures and explanations for those who may be considered a layman when it comes to chemistry and biology:
Here is the amino acid Glycine:

Here is the amino acid Proline:

Here is the complete Noopept molecule:

Here is a breakdown and explanation of what is where and what is what within the Noopept molecule:

So, what does this mean and how does it all add up? Well, first of all, peptides when administered orally are rendered, for the most part, useless. This is because digestive enzymes and acids will rip apart the polypeptide (AKA a protein) into its individual amino acids for use. This is why we cannot ingest HGH, IGF-1 or any of these long-chain amino acids. They are too large to enter the gated channels in the cells lining the GI tract to be absorbed, so they must be broken apart into their smaller amino acids and be taken into the body that way. What results is a peptide that is no longer functional because it got ripped apart and digested. Now, smaller peptides such as Noopept and single-amino acid molecules such as T3 (Triiodothyronine) are absorbed at a much higher rate because of how small the peptide chain is (T3 is simply one amino acid with iodine atoms attached to it, and Noopept is just 2 peptides large with an ester attached to it). Alright, we already know these details, so what? Well here is what: a certain percentage of peptides usually make it through the GI tract into the bloodstream intact (especially small ones like Noopept). However, every individual is different in how they process different foods, medications, and compounds, and so and there are a large variety of enzymes that break the bonds between amino acids in peptide chains into the individual amino acids. When it comes to peptides, it then presents an issue as to how to generate an effective solution for dosing. This is whyother methods of administration are used. When it comes to the REALLY big peptides like HGH, IGF-1, etc. they must be injected (or nasal sprays, etc.) and there also exist transdermal administration for other peptide-based bedications. For small ones like Noopept, individuals can use sublingual administration for increased absorbtion. But how does this work? And how does Noopept still retain oral bioavailability in the GI tract? Well, it's time to delve deeper into that!
One must understand that if a specific percentage of Noopept (or any compound) demonstrates bioavailability through the GI tract and crosses the blood brain barrier unchanged, it doesn't mean that it underwent 100% absorbtion. Compounds like Noopept do not require 100% absorption to operate efficiently due to the fact that this is SUCH A STRONG RACETAM (1,000 times STRONGER than the strongest Racetam that was around before it). Now here is the other thing, in addition to having a certain percentage of it absorbed through the GI tract, any additional Noopept that was not absorbed in this manner will continue on to the hepatic system (the liver) and undergo hepatic metabolism where it may be broken down in the liver into metabolites, BUT this would not affect the Noopept that did cross the blood brain barrier, because it remains unchanged by hepatic metabolism (the amount that gets through to the blood brain barrier intact does not reach the liver at all as it avoids the first pass).
It is very important to understand that Noopept's mechanism of action is that of a pro-drug. NOOPEPT DOES NOT DO ANYTHING DIRECTLY. Its metabolites are the active drugs that do the work. What this means is that the administration of Noopept seems to increase the concentration of an endogenous Nootropic in the nervous system known as Cyclo-L-prolylglycine(3). If you still don't understand what this means, it is basically the same idea as prohormones or HGH. When exogenous HGH is administered, its half life is extremely short but the mechanism of action of HGH is that it signals the liver to release large amounts of IGF-1, which is the hormone that actually does the work that is commonly credited to HGH. Similar concept with Noopept. Noopept could be considered a propsychotropic just like how 1-androstenedione is a prohormone. REMEMBER THIS! IT IS VERY IMPORTANT!
The Noopept molecule as a whole, from what I have been able to gather from my research, works like this: The section of the Noopept molecule that seems to actively provide the effects of Cyclo-L-prolylglycine increases is most likely the Racetam part of the Noopept molecule (the 2-Pyrrolidone ring), and if you don't know what that is then just scroll up and look at the Noopept molecule. The 'Racetam' part of the molecule is the four corner ring with the Nitrogen (N) atom right at the top center of it (this ring is officially known as a 2-Pyrrolidone ring in chemistry). This ring is the one common structural characteristic among all Racetams that make Racetams a Racetam. Just like how all anabolic steroids possess the basic four-ring carbon structure known as the steroid structure - this is what makes a steroid a steroid. Now, Noopept may also work on Glycine receptors using the tail end of the Noopept molecule as well (the tail end if you take a look at the picture IS the Glycine amino acid). The whole Noopept molecules does need to be intact for it to do its job. Individually ripped apart Glycines, Prolines, and Phenylacetyl esters floating around won't do anything in the body - its like ripping a car apart into individual nuts, bolts, and scaps of metal. It's not even a useable car at that point!
So, the question is: Oral or sublingual administration?
ORAL: Conclusion is that a good portion IS absorbed orally, while a good portion is also destroyed by enzymes and hepatic metabolism. The reason why Noopept still works so well even when ingested orally is because it's such a powerful compound (remember, 1,000 times more potent than Piracetam, which was the strongest Racetam that was around before the discovery of Noopept).
SUBLINGUAL: You will absorb almost 100% through this route. Not much else to be said here. No risk of any percentage of it getting ripped apart by hepatic metabolism, as it avoids the first pass. KEEP IN MIND THAT DOSING NOOPEPT IN THIS MANNER WILL RESULT IN FAR STRONGER AND MORE POTENT EFFECTS IN COMPARISON TO ORAL ADMINISTRATION OF THE SAME DOSE (30mg orally vs 30mg sublingually will = far stronger effects sublingually), AND THEREFORE A LOWER DOSE MAY BE NECESSARY DOING THIS.
However, at the end of the day, the fact of the matter is this: people who take decide to take Noopept or racetams that are waiting to expect some massively huge effect need to drop the Noopept and look somewhere else. Racetams and Noopept cause changes that many people just take for granted or will not truly notice. You have to not only be in proper tune with your body and its reactions, but you also need to engage your brain in constant learning stimulus to really notice the difference between after taking Noopept and before you started. These effects from Noopept, as I have said MANY TIMES, are cumulative (meaning, they build-up slowly over time just like AAS and you cannot expect 'gains' within the first week or two of use)! I cannot hammer that point enough into everyone's heads here. DO NOT expect anything short-term wise from Noopept unless you are a very sensitive responder. My effects did not reach a higher level of effects until at least 2 weeks into use.
REFERENCES:
1. Pharmacokinetics of new nootropic acylprolyldipeptide and its penetration across the blood-brain barrier after oral administration. Boiko SS, Ostrovskaya RU, Zherdev VP, Korotkov SA, Gudasheva TA, Voronina TA, Seredenin SB. Laboratory of Pharmacokinetics, Institute of Pharmacology, Russian Academy of Medical Sciences, Moscow. Bull Exp Biol Med. 2000 Apr;129(4):359-61.
2. Bioaccessibility of the new dipeptide nootropic drug noopept. S. S. Boiko, V. P. Zherdev, T. A. Gudasheva, R. U. Ostrovskaya, S. A. Korotkov, O. Yu. Kravtsova. Khimiko-Farmatsevticheskii Zhurnal, Vol. 38, No. 12, pp. 3 – 5, December, 2004.
3. "The major metabolite of dipeptide piracetam analogue GVS-111 in rat brain and its similarity to endogenous neuropeptide cyclo-L-prolylglycine". Gudasheva TA, Boyko SS, Ostrovskaya RU, Voronina TA, Akparov VK, Trofimov SS, Rozantsev GG, Skoldinov AP, Zherdev VP, Seredenin SB (1997). European Journal of Drug Metabolism and Pharmacokinetics 22 (3): 245–252. PMID 9358206