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NDMA Agonist

Oddeye

Oddeye

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Joined
Nov 19, 2006
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It has been previously shown that NMDA is toxic to cell. What exactly I want to know is what are the NMDA Agonist are and which one are considered safe (I am guessing that it is possible to reverse the toxicity)

From wikipedia : Activation of NMDA receptors results in the opening of an ion channel which is nonselective to cations. This allows flow of Na+ and K+ ions, and small amounts of Ca2+ .

I have just read an acceptable amount of information about those receptor and from what I read when they are activated it greatly improve the brain to form memories (long term memory/apparent to learning when young).

Wikipedia list a tons of antagonist but no agonist. I really find it promising, well thanks in advance. Feel free to just discuss.
 
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^F&B, your missing the point: this discussion is about agonists not antagonists.
 
Wikipedia says that it is believed that nootropics of the racetam family (piracetam, etc) are believed to have an effect on NDMA receptors, which would probably be agonist in action if agonists increase learning ability/memory formation. This is an uncited claim though but I imagine some perusual through the primary literature would bring up some studies on the like.
Anecdotal reports on erowid suggest that piracetam inhibits the effects of ketamine. I've found similar results although it was a very uncontrolled study.
my 2 pence
 
ebola? said:
but are these excitotoxins?

ebola
Click to expand...


i'd wager a guess that a lot of the full spectrum agonists are... the ones with selective affinities for different subtypes may not be.
 
NMDA agonists are often quite potent convulsants and in large doses are neurotoxic. I doubt that the racetams if they work at all as nootropics are operating through simple NMDA agonism, more likely they are acting through the cholinergic system.My gut feeling is that the racetams are simply not toxic enough to be acting as NMDA agonists. It also isn't as simple as an agonist counterating an antagonist: multiple binding sites etc.
there are quite a few potent and selective NMDA agonists for example the cyclobutyl analog of gutamate : trans ACBD.
 
Wow, that sounds like a nightmare to me!

I suppose these things would be used as torture devices.

But just a note from personal experience: Nefiracetam and Oxiracetam almost completely block the effects of Ketamine, whether through glutamate agonism or some other way. And I'm talking 100mg Ketamine IV after taking the above drugs - all that happened was a weak rush and vague feeling of ketamine that lasted not longer than 5 mins.

I will add another note. I noticed this even before I realized that racetams block ketamine:

Some of you are aware of my passion about Ketamine being the miracle cure for my horrific, morbid depression and anxiety.

Surprise surprise - both of the racetams I tried created an unmistakable and severe shift to a negative mood!!
 
Jamshyd said:
Wow, that sounds like a nightmare to me!

I suppose these things would be used as torture devices.

But just a note from personal experience: Nefiracetam and Oxiracetam almost completely block the effects of Ketamine, whether through glutamate agonism or some other way. And I'm talking 100mg Ketamine IV after taking the above drugs - all that happened was a weak rush and vague feeling of ketamine that lasted not longer than 5 mins.

I will add another note. I noticed this even before I realized that racetams block ketamine:

Some of you are aware of my passion about Ketamine being the miracle cure for my horrific, morbid depression and anxiety.

Surprise surprise - both of the racetams I tried created an unmistakable and severe shift to a negative mood!!
Click to expand...

Considering one would be non-toxic, it could be combined with aspirine or any other pain meditation. Not to mention that NMDA block tolerance from opiate. It would allow to learn very deeply just like when you were young, possibly cure some mental disorder by relearning.
 
Yeah i found piracetam counteracted the effects of ketamine quite considerably, so not good to take them together as its a waste of good k, but the piracetam is great the morning after when your head still feels all fuzzy from the k you had the night before! Gets you thinking properly again in no time...
 
Well, the huge (and seemingly equally useless) ammount of research on racetams usually claims that they "potentiate NMDA currents".

I never found reading research on racetams useful since the results are always tentative and a lot of unnecessary info seems to be constantly regurgetated.

Would "potentiating NMDA currents" mean that the racetams are agonists indeed? Or could it be indirect?

I think 90% of the racetams' claimed effects are nothing but placebo (IME). So now they are on my drugs blacklist (I actually never had a drug blacklist untill I expeimented with the racetams and GHB - ironically, two substances that got more hype than they deserve!).

I'm not dissing nootropics though - I do find Vinca derrivatives, L-theanine and Huperzine-A useful for both recovering memory failure due to benzo addiction, AND some mood lift. It is nothing huge, but I certainly find that these three substances, especially when combined, seem very beneficial.

Why did I just make a paragraph that looks like an ad? Well guess what, all three (well, four - by vinca derivatives I mean Vincamine or Vinpocetine) have at least one thing in common: they all have an antagonistic effect on NMDA!

I am very sure that I've read the above in some researxchm, but I an not currently in the best mindset rigt now to be able to find the refs, but I will eventually. If anyone has them or is kind enough to do a search, then all the better :).
 
Oddeye said:
Considering one would be non-toxic, it could be combined with aspirine or any other pain meditation. Not to mention that NMDA block tolerance from opiate. It would allow to learn very deeply just like when you were young, possibly cure some mental disorder by relearning.
Click to expand...

Sorry I just noticed this.

I am sick at the moment so my mind is probably clouded (and adding valium doesn't help ;)). But I simply do not understand your sugestion, or how it relates to my post that you were replying to.

Could you please elaborate?
 
Ok Jamshyd, what I was saying is that an Agonist of NMDA that would be non-toxic would allow you to have the capacity to make new memories that have the strenght of those when you were young. Meaning the newest memories have the same impact on the mind than those you made when your brain was growing. It has great application in the field of mental illness, allowing you to live another situation twice and have a good feeling about it where you previously had a bad one.

On a second note, NMDA induce the tolerance to opiate and many other drugs. The side effect of activation of NMDA is that it enhance sensivity in many ways, including pain. Using aspirine in combination with NMDA would allow this kind of learning.

NMDA can create a depression feeling, the depression come from an enhanced sensivity to everything. Meaning if you cut your finger, you'll feel the pain during long and you will recall it for a pretty damn long time. The NMDA is expressed when you are young, remember how much it hurted when you fell off your chair from the first time? Remember how you remember it. (Meh not the best exemple but whatever)

And so, racetam are not placebo, this would explain why people have enhanced memories (to some extend) on them and why you fucking hate them.

Well I hope you understood what I meant, if not feel free to post again I will try the best to explain you more.
 
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There are some strange SAR's in this class of compounds, a lot of room for exploration for agonists, the pharma companies that have generated some of the newer antagonists have probably run across a few agonists, maybe you can ask them to open up their notebooks for you :P
on another note, clicking on the link for memantine in the NMDA wiki page brings up a beautiful structure, that of the adamantanes. trippy.
and thats been another useless post from KA.
 
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