Comment · Mon, May 4, 2020 · Natrium Health & Nootropics Depot
Agmatine 2.0
Original post in this thread
vertigho · 11 points
Hi, I posted here about my experience with agmatine sulfate and kratom in late-October 2019. The story I described went as follows (please note I had been taking kratom for \~2 years prior to taking the agmatine):
1.) I took \~1.50g agmatine on two separate occasions over the course of 2-3 days, with the intent of simultaneously reducing my kratom dose ... I didn't reduce my kratom dose (which in hindsight may have been a mistake).
2.) following these agmatine doses, I ceased agmatine and continued taking kratom at my normal amount.
3.) since taking the agmatine, my emotional range, euphoria experienced via kratom (and euphoria experienced in general), and general sense of color in the world has been completely stunted. I was optimistic this would clear with time away from agmatine, but no-dice.
Fast forward 7 months to now, I am still feeling a different baseline mood and different reaction to kratom than I was pre-agmatine. Another thing I've noticed is that time seems to move faster in a very subtle but consistently noticeable way, and I often have a headband-like pressure headache, most noticeable on the sides of my head, and I often feel an emptiness in the front of my he…
What they were answering
Eclias · 1 points
From what I'm reading Agmatine has been ruled out as a GluN1 or GluN2 ligand and is showing binding only at the mk-801 site within the channel itself, so I don't think throwing an NMDA PAM at it will help by itself, it would just open a blocked channel but still no influx. I'm assuming (which is dangerous if course) that, similar to mk-801, agmatine remains bound inside the channel after the receptor closes, so the NMDA channel would need to be reopened to speed removal of PCP/MK-801 binding ligands, so on that note I could see a PAM helping if it were day-of or day-after, but that effect is usually on the order of hours or days. I can't imagine it being a direct factor 7 months in.
In the event the Agmatine has somehow made some sort of permanent home in a number of now-desensitized NMDA receptors, I'm wondering if something crazy like magnesium depletion plus a glutamate flood plus Sarcosine might have any effect. But again 7 months in I can't imagine it still being a direct effect. I'll have to keep reading up on Agmatine NMDA MoA.
I'm more inclined to think something has disturbed endogenous Agmatinergic tone somehow, which I'm still unclear on how exactly that's regulated.
Edit to add: magnesium depletion is apparently the exact wrong thing to do when looking to clear mk-801 pore blocks but my point was that th…
u/MisterYouAreSoDumb · Natrium Health & Nootropics Depot
It looks like agmatine enhances the potency of MK-801. So I am not sure they are binding to the same site.
https://www.ncbi.nlm.nih.gov/pubmed/25553821
It looks like agmatine is a very selective antagonist at a polyamine bindings site of the NMDAR.
https://www.ncbi.nlm.nih.gov/pubmed/12363406
It also looks like things that bind to the polyamine site on the NMDAR are anti-depressant.
https://www.ncbi.nlm.nih.gov/pubmed/8545484
This is a really good paper on that site: https://www.ncbi.nlm.nih.gov/books/NBK5272/