Comment · Fri, August 21, 2015 · Ceretropic
Four(-ish) questions about NA-Selank!
Original post in this thread
srubek · 10 points
ONE
It is widely accepted that NA-Selank's calming properties are attributable to its "induction of the metabolism of serotonin," right?
So my first real question is, what does that mean? Does it induce metabolism of serotonin into serotonin metabolites; or does it metabolize potential precursors into serotonin itself?
If the answer is the latter, then does this result in a net increase in serotonergic synaptic activity, or just an increase in synthesis & storage of it in the presynaptic vesicles?
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TWO
I'm also curious by what all mechanisms this is considered a nootropic...
So secondly, is its release of BDNF/NGF exclusive to the hippocampus?
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THREE
I've noticed that NA-Semax Amidate has an anxiolytic component to it; an effect that its non-amidated version is missing...and I would like to have that anxiolysis at night but without Semax's stimulation...hence my third big question:
Would it potentially be more effective, anxiolytic, and/or longer lasting with an 'amidated' C-terminus or other...terminus? (please forgive and correct my technical errors--I prefer precision, and…
What they were answering
Direct reply to the original post — see the thread post above.
u/MisterYouAreSoDumb · Ceretropic
1) N-Acetyl Selank's anxiolytic mechanism is related to its ability to inhibit enkephaline-degrading ezymes. That increases the levels of your body's natural opioids. That inhibition modulates the dopaminergic system, and prevents hyperactivity arising from excess dopamine. That is one of the main mechanisms for its anxiolytic effects.
Selank also prevents increases in serotonin in the frontal cortex, hypothalamus, and amygdala. This is postulated to be due to its ability to decrease the synthesis of serotonin, or to increase its metabolism. That may play a role in the anxiolytic effects as well. It would be a net decrease in serotonergic activity.
2) The nootropic qualities are due to the tripeptide sequence on the C-terminus, which is Proline-Glycine-Proline. That same sequence is on the end of Semax as well. It also is very similar to the dipeptide end of Noopept, which is Proline-Glycine. Noopept adds a phenylacetyl group to the dipeptide sequence, to protect it from enzymes, and make it more orally bioavailable. The Proline-Glycine (PG) and Proline-Glycine-Proline (PGP) sequences are what lead to increases in BDNF and NGF expression in the hippocampus. That increase in neurotrphic factors is the main "Nootropic" effect of Selank, Semax, and Noopept.
3) That anxiolytic effect is most likely due to increased permeability of the peptide, leading to more enkephaline enzyme inhibition. The same modification can be done to Selank. Our lab is working on N-Acetyl Selank Amidate right now. The modification neutralizes the charge of the peptide, and protects the C-terminus from degradation as well. I am starting to acetylate and amidate many peptide. N-Acetyl Epitalon just arrived, and N-Acetyl Epitalon Amidate is on the way. I am also playing around with amidation of other amino acids, to improve their BBB permeability.
4) It's not that they differ. It's more that the modifications allow for higher amounts of the peptide sequence to reach the brain, and alter the charge of the peptide. Until we do some animal studies, we are going to have to speculate about the specifics, though.