Semax

links: Nootropics Neuropeptide reference: https://en.wikipedia.org/wiki/Semax 10-18-2021

Semax #

Met-Glu-His-Phe-Pro-Gly-Pro. We go deeper down the iceberg… invented in mother Russia in the 1980s.

• Its mechanism of action is unclear. May act through Melanocortin Receptors which has an inhibitory action on D2 I believe.

• Increases TrkB insofar as the Adrenocortocotropic Hormone system is working well. I think it basically mimics ACTH-10.

  • Downregulation warrants cycling.

• Antidepressant and axiolytic; attenuates behavioral effects of chronic stress.

• Semax and Selank Inhibit the Enkephalin-Degrading Enzymes of Human Serum

• Semax, an analog of ACTH(4-10) with cognitive effects, regulates BDNF and trkB expression in the rat hippocampus

  • 50μg/kg (HED 581): 1.4-fold increase of BDNF protein levels accompanying with 1.6-fold increase of TrkB tyrosine phosporylation levels, and a 3-fold and a 2-fold increase of exon III (gene thing) BDNF and trkB mRNA levels, respectively, in the rat hippocampus
  • Upregulates TrkB, unlike noopept. I mean think about it, that’s probably why it has reverse tolerance. The question of course is how long that lasts (I haven’t even read the paper yet xd) especially if you ragequit after you notice shedding and your shit is still upregulated.

• Effects of Semax on Dopaminergic and Serotoninergic Systems of the Brain3: a: hypothalamus, b: striatum. 1: control, 2: 0.15mg/kg ip after 30 mins, 3: 120 minutes.

  • For the fans: Yeah decent increase in Hypothalamus Dopamine concentrations. Looks like a MAO-B inhibitor would do it well considering the dopac+HVA increase but this is probably the case with literally anything that increases dopamine to be honest. Basically no increase in 5-HT but a spike in 5-IAA I believe is a nice sign?

• 515mcg. Another study showed 50% decrease in frontal cortex BDNF expression.

Supplementation #

• It’s actually stable <100g°F for quite a while… but jus refrigerate it.

Forms #

• (The addition of -acetate is just for the sake of stability.)

• Semax

  • Large half-life variability.
  • Dose: Anywhere between 100μg-3mg.

• N-acetyl-semax is four amino acids long.

  • Debonaire: NA-Semax is my fav. The amidated version was just too strong for me, caused GI effects I didn’t like (Gastroparesis: delayed gastric emptying; weak peristalsis causing food to remain in the stomach for prolonged periods)
  • Dose: A bit less than semax. Probably half.

• N-Acetyl-Semax-Amidate: ~33% longer half-life.

  • The amidate seems to negate some of the overstimulation of the n acetyl semax and feels much more BDNF-like.

• Adamax: 2x the half-life of NAS and better absorption.

• The reverse tolerance is with its nootropic effect, for the most part. The stimlation may build tolerance, thus ’tolerance’ might be more pronounced with NAS/NASA but I’m quite sure it doesn’t mean anything is downregulated.

Anecdote #

• NASA is anxiolytic. NAS is maybe anxiogenic.
• I’ve been feeling dumber on semax. It makes me happy and alert but I’m getting major mental lag; creativity and verbal fluency is down. I feel like semax would be optimal for meditation since my hyperactivity is completely amputated…
• Significantly enhances vigilance, motivation, wellbeing.
• Mixed responses on clarity
• Best taken alone. Potentiates stimulants.
• Dude on RPF said it gave him serotonin syndrome. The hell?
• They say it makes you sleepy, yet just as many people talk about insomnia.

Semax, An ACTH(4-10) Analogue with Nootropic Properties, Activates Dopaminergic and Serotoninergic Brain Systems in Rodents (Eremin et al., 2005) #

• 0.15mg/kg
• The Pro-Gly-Pro fragment of Semax is responsible for its metabolic stability and the relatively long duration of effects
• Its structure is based off Adrenocortocotropic Hormone. Unclear mechanism, but possibly melanocortin receptors antagonism - α-MSH at MC4 and MC5, not MC3. MC1/2 unknown. R Yeah Fig. 3 is coadministration with Dextroamphetamine but that’s some seriously impressive potentiation.
• It is generally accepted that the concentration of 5-HIAA , a metabolite of 5-HT, rises with an increase in the 5-HT, which may reflect an activation of the brain serotonergic system. Reverse tolerance! Especially vanilla semax.