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Nootropics Smartdrugs, Brain boosters & Cognitive enhancers.

 
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  #1  
Old 16-11-2010, 18:23
Synesthesiac Synesthesiac is offline
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Huperzine A - Nootropic or "acetylcholinesterase inhibiting neurotoxin?"

Ok there seem to be many good things written about this. For example (from this site)
Quote:
L-Huperzine

A is a natural plant alkaloid (extracted from Huperzia serrata), which quickly and potently boosts memory, learning, and concentration. Used worldwide for decades in adults and high school students. Is considered the most potent short term memory enhancer available.

Biochemical Effects
  • Potently raises Acetylcholine (main memory neurotransmitter) by inhibiting its breakdown from Acetylcholinesterase.

  • Strengthens the Brain's NMDA receptors (Enhances Focus, Learning, and Brain Functioning)
Dose
Take 200-400 mcg daily for best results with meals.

When can I feel it?
Works within an hour to a few days.

And there's other information about it elsewhere:

Quote:
Huperzine A is an acetylcholinesterase inhibititor and NMDA receptor antagonist, although the latter effect is not usually observed within clinically relevant dosages in humans.

Huperzine A has also attracted the attention of US medical science. It is currently being investigated as a possible treatment for diseases characterized by neurodegeneration – particularly Alzheimer’s disease. It has been found to be an inhibitor of the enzyme acetylcholinesterase. The structure of the complex of huperzine A with acetylcholinesterase has been solved by X-ray crystallography (PDB code: 1VOT; see the 3D structure).This is the same mechanism of action of pharmaceutical drugs such as galantamine and donepezil used to treat Alzheimer's disease. Huperzine A is also a NMDA receptor antagonist which protects the brain against glutamate induced damage, and it appears to increase nerve growth factor levels in rats.

Clinical trials in China have shown that huperzine A is comparably effective to similar drugs on the market, and may even be a bit safer in terms of side effects.[citation needed] The National Institute on Aging has completed a Phase II clinical trial to evaluate the safety and efficiency of huperzine A in the treatment of Alzheimer's disease in a randomized controlled trial of its effect on cognitive function. It has also been investigated for its effectiveness against epilepsy in an initial 20-person clinical study by Harvard University neuroscientists examining its worth and side effects in those who are not satisfactorily treated by existing pharmaceuticals.

Possible side effects include breathing problems, tightness in the throat or chest, chest pain, skin hives, rash, itchy or swollen skin, upset stomach, diarrhea, vomiting, hyperactivity and insomnia. Most adverse events were cholinergic in nature and no serious adverse events occurred. Huperzine A is a well-tolerated drug.
But, I stumbled across this snippet from another forum online and was unsure whether it was a valid criticism or not.

http://brainmeta.com/forum/index.php...dpost&p=108083
Quote:
ACHe is there for a reason. Inhibiting ACHe long term will basically give you mild brain damage, roughly equatable with excitotoxicity of high glutamate/NMDA doses, seratonin syndrome (or any toxic accumulation of molecules as a byproduct of inhibited metabolism). Also I'm not sure how much I trust the OP's study: roughly "Huperzine A also protects from damage by the experimental neuro toxin NMDA." Ok, NMDA isn't an "experimental neurotoxin". It's a receptor that you can't function without, and an amino acid that mimics glutamate (and can therefore be excitoxic just like glutamate can).

Huperzine A is an NMDA antagonist. You know what else is? Ethanol. Chronic administration of ethanol causes brain damage through precisely this pathway (not the only one however). So yes, it protects from excitoxicity, which you will pretty much only have if you have a stroke or a seizure, but it does this by inhibiting glutamate-affected signalling, which plays a major role in brain plasticity, learning and memory. The brain upregulates NMDA receptors in response to its antagonism, but this is not a good thing. Huperzine A will, over time, increase NMDA desensitization and kill your ability to learn information.

It is also a potassium antagonist. You know what else is? Lamictal, and I can tell you from personal experience that chronic lamictal administration absolutely destroys your memory. Don't take my word for it, look up K+ role in synaptic transmission.

Huperzine A is most likely not safe long term. Ache inhibitors are potent neurotoxins. I believe black widow poison is ache. Serin gas is an ache inhibitor. So taking highly purified huperzine A is not the same safe medicine that the Chinese use for short term administration (in far smaller doses) in traditional medicine. I'd be very careful, and evaluate how long I want to live a healthy lifestyle. ACHe inhibitors have been on the market for a long time, and they have a side effect profile to die for.
Scare tactics? Or valid point?

Last edited by Synesthesiac; 16-11-2010 at 18:29.
  #2  
Old 19-02-2012, 05:21
sambocyn sambocyn is offline
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Re: Huperzine A - Nootropic or "acetylcholinesterase inhibiting neurotoxin?"

mostly scare tactics, but something worth looking into...

"ACHe is there for a reason. Inhibiting ACHe long term will basically give you mild brain damage, roughly equatable with excitotoxicity of high glutamate/NMDA doses, seratonin syndrome (or any toxic accumulation of molecules as a byproduct of inhibited metabolism)."

um, no. citations?

"Ok, NMDA isn't an "experimental neurotoxin"".

yes it is. the NMDA receptor is a glutamate receptor subtype that selectively responds to the synthetic excitoxin. (wikipedia NMDA#Biological_function)

"Huperzine A is an NMDA antagonist."

interesting.

"The brain upregulates NMDA receptors in response to its antagonism, but this is not a good thing. Huperzine A will, over time, increase NMDA desensitization and kill your ability to learn information."

these two statements are inconsistent, i think.

"Huperzine A is most likely not safe long term. Ache inhibitors are potent neurotoxins."

not all are. many are therapeutic, like huperzine a. (wikipedia AChEI#Examples)
  #3  
Old 20-02-2012, 09:27
dae141 dae141 is offline
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Re: Huperzine A - Nootropic or "acetylcholinesterase inhibiting neurotoxin?"

There is a saying: "the dose makes the poison" and it is probably relevant here. Just because inactivating huge amounts of the brain's ACHe is bad doesn't mean doing so for a small amount is necessarily very dangerous.
  #4  
Old 27-08-2012, 23:40
Impure157 Impure157 is offline
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Re: Huperzine A - Nootropic or "acetylcholinesterase inhibiting neurotoxin?"

Quote:
Originally Posted by sambocyn View Post
"The brain upregulates NMDA receptors in response to its antagonism, but this is not a good thing. Huperzine A will, over time, increase NMDA desensitization and kill your ability to learn information."

these two statements are inconsistent, i think.
As I have been taking Huperzine A as a treatment for an autoimmune disorder I have, moderate cases of which are treated with acetylcholinerase inhibitors, I've been researching it fairly extensively. With that said, the mechanism described by sambocyn in the quote above is something that can occur in various pathways in the brain. I understand how it seems contradictory but it's been shown that in response to excessive antagonists binding to certain receptor sites there will be an increase in the concentration of the receptors at that site. This causes the brain to become desensitized to whatever will bind to the receptors at that site, as the increased receptor concentration means more of what activates them will be required to produce a response. Usually this increase can be reversed by abstaining from whatever the antagonist was, but after long periods of upregulation at those sites that may not be the case.

P.S. I know this has been proven to occur at a few receptor sites (such as the NMDA receptors or the D2 dopamine receptors) from various drugs and psychological disorders, but where else this can occur in the brain I have no idea.
  #5  
Old 18-06-2013, 22:07
joefear joefear is offline
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Re: Huperzine A - Nootropic or "acetylcholinesterase inhibiting neurotoxin?"

So what about Rivastigmine?
Does anyone have any experiences with this?
  #6  
Old 24-06-2013, 02:55
Shampoo Shampoo is offline
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Re: Huperzine A - Nootropic or "acetylcholinesterase inhibiting neurotoxin?"

For what it's worth, the concerns regarding Huperzine A as an NMDA-antagonist are likely irrelevant. Most individuals dose Huperzine at 200-500µg, which should produce a plasma concentration of well below 0.05µM. The IC50 for NMDA antagonism is >45µM. Any dose which would cause Huperzine A to act as an NMDA antagonist would cause a slew of side-effects related to excessive ACh well before that.

As for Huperzine A as a potential neurotoxin, this is going to be dose-related - any AChEI will cause some neurotoxicity at large doses. Considering that the plasma concentration required for effective AChE-inhibition could be achieved by an oral dose of 50µg, I think keeping doses in a reasonable range would reduce the probability of neurotoxicity to about zero - though, obviously with the lack of studies in healthy human volunteers, this is all speculation.

Post Quality Evaluations:
awesome post. great info, thanks
  #7  
Old 04-07-2013, 06:40
sambocyn sambocyn is offline
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Re: Huperzine A - Nootropic or "acetylcholinesterase inhibiting neurotoxin?"

Quote:
"The IC50 for NMDA antagonism is >45µM"
citation?


if what i know of neuropharm is right, IC50 is a property of drugs, not receptors.

IC50 measures the toxicity of a drug. NMDA antagonism is the effect, the molecule is the cause. if Huperzine A were a very potent NMDA antagonist, it could have a very low IC50.

saying not to worry on that reason doesn't seem safe.
  #8  
Old 07-07-2013, 17:12
DiabolicScheme DiabolicScheme is offline
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Re: Huperzine A - Nootropic or "acetylcholinesterase inhibiting neurotoxin?"

Is actually sounds like a possibility when you consider down-regulation/up-regulation happens to other receptors in the brain.

However, take antipsychotics for instance; if used for a short period to blockade dopamine wouldn't the brain up-regulate dopamine and if this were the case wouldn't antipsychotics be a novel substance to reverse amphetamine tolerance?

What I'm getting at is that I don't believe every receptor responds with up regulation; I'll have to do some more reading about the functioning of the NMDA receptor.

If this is the case this means things like DXM would also increase the likely hood of brain damage with regular use.
  #9  
Old 07-07-2013, 22:18
Shampoo Shampoo is offline
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Re: Huperzine A - Nootropic or "acetylcholinesterase inhibiting neurotoxin?"

Quote:
Originally Posted by sambocyn View Post
citation?
Wang XD et al, 1999. Modulation of NMDA receptor by huperzine A in rat cerebral cortex. Or Zhang JM & Hu GY, 2001 (they found a higher IC50).
Quote:
=sambocyn;1324234if what i know of neuropharm is right, IC50 is a property of drugs, not receptors.
Correct, IC50 is a basic pharmacological term which identified the concentration of a drug necessary to exhibit half-maximal inhibition in vitro. It is often used as a starting point for identifying in vivo concentrations.
Quote:
Originally Posted by sambocyn View Post
IC50 measures the toxicity of a drug. NMDA antagonism is the effect, the molecule is the cause. if Huperzine A were a very potent NMDA antagonist, it could have a very low IC50.
IC50 has nothing inherently to do with the toxicity of a drug. It is a measure of effectiveness, not toxicity. Huperzine A is not a potent NMDA antagonist, that was the whole point.
Quote:
Originally Posted by sambocyn View Post
saying not to worry on that reason doesn't seem safe.
The point is that the concentrations at which it can act as an AChE inhibitor are much lower than those where it begins to impact NMDAR function directly. So the doses for these two effects are far apart, and achieving the latter (NMDA antagonism) would mean being at hundreds of times the necessary dose for AChE inhibition, which would present far more problems than the NMDA antagonism.
Quote:
Originally Posted by DiabolicScheme View Post
Is actually sounds like a possibility when you consider down-regulation/up-regulation happens to other receptors in the brain.
All receptors can respond with up- or downregulation in response to inhibition/excitation, respectively. Presynaptic release mechanisms can also be altered in response to excessive inhibition/excitation. This is standard across biological signaling machinery.
Quote:
Originally Posted by DiabolicScheme View Post
However, take antipsychotics for instance; if used for a short period to blockade dopamine wouldn't the brain up-regulate dopamine and if this were the case wouldn't antipsychotics be a novel substance to reverse amphetamine tolerance?
Potentially, sure - but you would have to be targeting the same subtype of dopamine receptors, of which there are many.
Quote:
Originally Posted by DiabolicScheme View Post
What I'm getting at is that I don't believe every receptor responds with up regulation; I'll have to do some more reading about the functioning of the NMDA receptor.
NMDA receptors do upregulate in response to antagonists. This is well established. The point is that the NMDA-receptor antagonist effects of huperzine happen at such high concentrations that to achieve NMDA antagonism would be to far exceed the dose that would maximally inhibit AChE, which would be far more damaging.
Quote:
Originally Posted by DiabolicScheme View Post
If this is the case this means things like DXM would also increase the likely hood of brain damage with regular use.
DXM induces modest upregulation in both NMDA and D2 dopamine receptors.

Post Quality Evaluations:
well-researched, polite, and extremely informative. Thanks!

Last edited by Shampoo; 08-07-2013 at 15:11.

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