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Isochroma |
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#1
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Aspiring ![]() ![]() Group: Basic Member Posts: 61 Joined: Jun 22, 2008 Member No.: 24661 ![]() |
Piracetam Hydrazide On my quest to find Limitless's NZT-48, today I collected some documents about a piracetam derivative that has only been tested on lab animals called Piracetam Hydrazide: Piracetam Hydrazide {aka. 2-(2-oxopyrrolidin-1-yl)acetohydrazide} {aka. 2-(2-oxo-4-propylpyrrolidin-1-yl)acetohydrazide} The terminal NH2 of Piracetam is replaced by NH-NH2 to obtain the hydrazide - though that is not the synthetic route for its production. thallanylzirconio-methyl-tetrahydro-triazatriphenylene: Real or Fiction? "Piracetam derivatives with a hydrazide grouping in the side chain combine nootropic activity and a specific stimulant effect." - Study (see below for details) What interested me about this compound is not only that it hasn't been tested in humans, but that in rats it prevented hypoxia-instigated brain damage and even death - while piracetam did not. Due to the volume of material, I have bolded the sections of particular interest: Patent: (2-Oxo-pyrrolidines)-acetic hydrazides (1978) Description: ---------------------------------------------- After more searching I finally found a different paper on this novel molecule - this one containing a most thoroughly delicious paragraph which promptly stoked my fantasy of real NZT-48 into a flaming bonfire: "Piracetam and its 8 derivatives were studied in experiments on mice and rats with the use of standard neurotropic tests and nootropic activity tools. The electrophysiological index of GABA-ergic inhibition (the recovery cycle of cortical evoked potentials) was also investigated. It was shown that piracetam derivatives as well as piracetam itself have a pronounced antihypoxic activity and prevent the amnestic effect of electroshock in experimental passive avoidance. Most of them were inactive according to the standard neurotropic test. Piracetam derivatives with a hydrazide grouping in the side chain combine nootropic activity and a specific stimulant effect, while the derivatives possessing a phenyl ring combine nootropic and depressant activity.": Neuropharmacological properties of piracetam derivatives (1982)The depth of piracetam with the punch of a stimulant? The world awaits human tests. The Russians studied the racetams in a very different way from other institutions in other countries. Profit motive distorted by patentability and FDA concerns killed racetam research everywhere else. The Russians had no reasons to stop though... their orientation was purely pragmatic. To achieve the best possible function for applied programs - like their space missions. From that purely pragmatic approach came Phenotropil (Phenylpiracetam). This method - and goal - is the exact opposite of the ridiculously wasteful yet educationally incisive ITER energy program - a scientific gravy-train to nowhere whose only guarantee is that net-energy nuclear fusion will always be twenty-five years away from fruition. The Russians developed racetams like the Americans developed Apollo. Enough said. On to the next study: Piracetam Hydrazide boosts immune function: "Immunomodulatory effects of piracetam and a number of its derivatives were studied in mice. It was shown that multiple injections of such substances at a dose of 50-200 mg/kg change the amount of antibody-forming cells in the spleen of animals immunized with sheep red blood cells. The dose of 200 mg/kg was the most effective one, with the direction of immunomodulatory activity depending on the chemical composition of the compounds. Thus joining of phenol radical to piracetam molecule strengthened immunosuppression, and vice versa insertion of hydrazide group led to stimulation of antibody formation. It is stressed that immunosuppressive effect of piracetam must be taken into consideration during the clinical use of the drug": Effect of piracetam derivatives on antibody formation (1985): the Russians again.I shall wrap with the sweetest - or perhaps bitterest part - not only is this molecule unregulated, but three suppliers already have it for sale: Angene: 2-(2-OXOPYRROLIDIN-1-YL)ACETOHYDRAZIDE: RFQ sent by email 2011/07/03And for the adventurous a synthesis from UCB Pharma, the inventor of Piracetam: 2-Oxo-1-Pyrrolidine Derivatives, Processes for Preparing Them and Their UsesTo end, NZT-48 is the target so nicely painted in the film and its root work the novel - Illuminating the Dark Fields. It provides an ideal wishlist for the perfect nootropic and the name itself can also be appropriated - or expropriated - when we - or me - discovers a material both potent and powerful enough to take up the name without shame. When that day comes I will be handing out those magic clear pills and changing lives forever. To that end my next post will be on a very different yet similar subject: the substitution of certain atoms in the Piracetam molecule rather than the addition or subtraction of functional groups, in order to slightly modify the molecule's global electric field rather than produce the often overt, qualitative differences seen after additive functionalization. Dual rationales lie behind such an approach: first, we're already 90% there with Piracetam itself - and as such only a slight rekeying may be necessary to achieve spectacular increases in both efficiency and efficacy. Second, that the action of Piracetam is not based on chemical reaction but rather the influence of its global electric field on neighboring molecules. For a simple analogy, think of a drop of detergent in water - it does not react with water but by its mere presence modifies the eletronic functions of water molecules within its electropotential reach - drastically changing both the nanoscopic and macroscopic properties of said medium. More on this later. |
lucid_dream |
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#2
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![]() God ![]() ![]() ![]() ![]() ![]() ![]() Group: Admin Posts: 1713 Joined: Jan 20, 2004 Member No.: 956 ![]() |
Second, that the action of Piracetam is not based on chemical reaction but rather the influence of its global electric field on neighboring molecules this seems premature since the mechanisms underlying piracetam's effects have not been demonstrated. They most assuredly are chemical in nature. |
Isochroma |
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#3
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Aspiring ![]() ![]() Group: Basic Member Posts: 61 Joined: Jun 22, 2008 Member No.: 24661 ![]() |
I can assure you it is not premature. Both the lack of metabolism and lack of receptor binding support the statement. Recently very weak bindings have been found, but the weakness is such that this phenomenon is more association than 'binding'.
It has also been postulated that piracetam has effects on membrane fluidity, which I am in total agreement with. These effects - like that of detergent in water - occur because piracetam alters the cellular membrane by interspersing itself between the polar heads of fatty acid phospholipids - increasing membrane fluidity. Fish oil also does so because its omega-3 fatty acids are more flexible and thus fluidize the membrane while saturated and trans-fats stiffen the membrane and decrease its permeability. The main reason Piracetam's mechanism of action remains incompletely elucidated even today is because it is not something easy to quantify like receptor binding or a chemical reaction. Instead, its global electric field influences the molecules nearby and thus alters the biosystem in which it resides. Computational simulation of such large multi-molecule field interactions is far more complex than the simple binding of one molecule with another (aka. receptor interactions) or a chemical reaction. This is because any computational simulation must take into account the sum total of thousands or millions of electric fields in order that the totality behave as it does in reality. Even today's supercomputers are not up to the task. In contrast, the highly functionalized Piracetam derivatives Aniracetam and Pramiracetam are both metabolized and also - not coincidentally - have highly prominent receptor interactions. Aniracetam is metabolized to anisic acid and p-methoxyhippuric acid. This study shows that only 34.61% of orally administered Pramiracetam was excreted unchanged in dogs 72 hours after a single dose. Considering the short half-life of 2.3-3.9 hours also found in the study, and also considering that Pramiracetam is not stored in fatty tissues - the only logical conclusion is that the remainder - ~65.39% - was metabolized. Such interactions with mammalian metabolic systems further demonstrate that the highly functionalized Aniracetam and Pramiracetam indeed have chemically reactive 'hooks' and thus are also likely to exhibit stronger, more extensive and particularly de novo receptor interactions that Piracetam and Oxiracetam lack. The functional groups are so named because they literally 'functionalize' an otherwise 'nonfunctional' (aka. not-chemically-reactive) backbone. It's like the dfference between benzene and hexane or alkanes vs. alkenes or alkynes. Like a tree that has been artificially made to grow in one direction, racetam research has also received a particularly biased mode and directionality of investigation, so the results mirror the ability of researchers to understand within the context of their limited training and the requirements to obtain grants from institutions and approvals from the FDA: new molecules will only be tolerated if they can provide these. Thus the emphasis - to the near total exclusion of alternatives - of piracetam derivative research on receptor-targeted, easily understandable, easily computable and - not unexpectedly - chemically reactive functionalized versions. To this date only one Piracetam derivative defies the expansionistic-functionalistic formula: Oxiracetam, whose single extra oxygen atom modifies its effects in some ways slight and others significant - both quantitatively and qualitatively. Piracetam Hydrazide comes in a close second to Oxiracetam with a net addition of one Nitrogen and one Hydrogen. I believe the addition of these two atoms gives the hydrazide a running chance at retaining the important small-molecule characteristics of Piracetam with increased potency and perhaps altered quality - as tentatively indicated by at least one study quoted above. Only further testing - especially in humans - will answer these questions definitively. Piracetam and oxiracetam have also both been proved to not metabolize. Both are excreted entirely unchanged as confirmed by radiolabelling studies. I have the papers if you can't believe my words. The lack of metabolism is itself corroborative because the molecules are teflon-like: they have no electrical 'hooks' that can be easily grabbed and manipulated by any of the biomolecules located in mammals. The constant pursuit of adding functional groups to create or modify receptor ligation has been a half-mistake, because it has compromised the small-molecule's ability to alter membrane properties - in particular mitochondrial membranes - the restoration of whose function is crucial to correcting the fundamental result of aging-caused brain subfunction and outright dysfunction. The restoration of energy-conversion capacity increases the global function of the entire system without introducing a driving penalty as stimulants do. The size of the piracetam molecule is just as crucial as its geometric-electric field shape. For anything from the macroscopic to the nanoscopic detergent to the oily lubricant, the particle size allows or prevents interspersion at the correct distances and molar concentrations to have the desired fluidity effects. I am trying to look at the system as a mechanical engineer studying mixed-particle fluid flows, because the pure chemists have already had many decades to pursue their paths to exhaustion. My path is the one not taken: the questions unanswered, the methods untried. I will explain further in days to come. Now it's back to manga and research. |
Noopept-Power |
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#4
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Newbie ![]() Group: Basic Member Posts: 1 Joined: Jul 08, 2011 Member No.: 33424 ![]() |
Even if there is no study done in humans I'll be willing to buy some of it if CerebralHealth can synthesize it for a reasonable price. The pyrrolidine ring makes everything safe anyway.
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lucid_dream |
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#5
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![]() God ![]() ![]() ![]() ![]() ![]() ![]() Group: Admin Posts: 1713 Joined: Jan 20, 2004 Member No.: 956 ![]() |
The pyrrolidine ring makes everything safe anyway. I'm not sure what you mean by this, but if you attach cyanides or mercury to the pyrrolidine ring, it certainly won't be safe. I would be curious if chemists or pharmacologists have synthesized and systematically studied all (or many) chemical variations on the pyrrolidine ring, and classified or rated the chemicals according to cognitive effects. Does anyone know if this is the case or not, and where this information is located? |
Isochroma |
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#6
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Aspiring ![]() ![]() Group: Basic Member Posts: 61 Joined: Jun 22, 2008 Member No.: 24661 ![]() |
That information is, thanks to the Government, in the dusty files of private corporations who have no interest in releasing it. In fact, their interest is in keeping the data secret unless they can use it in a patent & product.
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Ralfy |
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#7
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Newbie ![]() Group: Basic Member Posts: 2 Joined: Jul 17, 2011 Member No.: 33453 ![]() |
I had to create this account to say THANK YOU Isochroma. I have read your posts, on this site and others, about nootropics and you have convinced me to start taking piracetam. I received my 500mg powder of Piracetam from SNS four days ago. At first I started with 1 gram and every day I've been increasing my dose by 100mg because I don't really feel the effect yet. I will increase my dose to 3 grams tomorrow. I just want to thank you for your informative and very descriptive posts. Please give me any advice you think I'll need. You're my nootropic sensei!
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Isochroma |
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#8
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Aspiring ![]() ![]() Group: Basic Member Posts: 61 Joined: Jun 22, 2008 Member No.: 24661 ![]() |
Thanks, Ralfy. Wish you the best of success on Piracetam - the alternatives are far more expensive and the non-racetam alternatives have more side effects and less legality. So let's all hope you can get something from the original :)
PS. Piracetam works much better with high-dose fish oil, as the two share complimentary properties. Also, do avoid any more than 500mg choline per day, or just use natural sources like egg yolk or meat. Choline overdose has nasty symptoms including depression and lethargy. Many folks who gave up on piracetam due to 'side effects' were actually driven from it by the excessive choline they took with it. For most individuals no extra choline - beyond a good diet - is needed. |
Ralfy |
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#9
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Newbie ![]() Group: Basic Member Posts: 2 Joined: Jul 17, 2011 Member No.: 33453 ![]() |
I've been on Piracetam for 6 days, still no effect. Today I took 5 grams of this stuff on an empty stomache, no effect... Whats wrong with me?
How can I become a producer of Piracetam? Any helpful websites? |
Isochroma |
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#10
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Aspiring ![]() ![]() Group: Basic Member Posts: 61 Joined: Jun 22, 2008 Member No.: 24661 ![]() |
Ralfy, there isn't enough wrong with you. That's the problem. Piracetam normalizes the brain's function and the more damage/aging the more the effects are shown immediately. When teens are given it and take a test a week or two later they score higher but virtually none will consciously notice a difference. They're mostly young and undamaged.
Everyone will still benefit but because you're healthier than some (myself included), the effects will be more subtle and take longer to manifest. You can also try the other racetams - Oxiracetam is your next best bet for an immediate effect. Aniracetam and Pramiracetam cause sleepiness for most. Try them all if you can afford them. For Piracetam the manufacturer recommends taking it for at least two weeks before testing or noticing a difference. All racetams are long-term builders so don't panic when it isn't an 'instant pill' like the toxic, addictive caffeine/amphetamines/name-your-poison here. Piracetam is mostly about support. Taking it means not getting tired when you would otherwise. It's harder to notice not being tired than it is to notice being stimulated. The first is a lighter shadow; the second a brighter light. That isn't as noticeable as, say, the highly obvious and nasty effects of a stimulant. Effects that tell you in no uncertain terms that you've taken a drug. Piracetam just isn't like that because it doesn't unbalance the brain's functions like stimulants/sedatives/hynotics/psychedelics do. So you have to look at the shadows getting lighter more than the sunlight getting brighter - get what I mean? Your knight in shining armor is there but he's working in the dark so you can't yet easily see him. |
superman |
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#11
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Newbie ![]() Group: Basic Member Posts: 1 Joined: Jan 13, 2013 Member No.: 34824 ![]() |
I'm sure you saw the movie Limitless. The drug in that movie..NZT. NZT is thallanylzirconio-methyl-tetrahydro-triazatriphenylene. Is that a real, possible medication/chemical compound to produce? I am 35 years old. In my younger years I did a ton of psychedelic drugs. LSD seemed to make me almost super intelligent. Obviously the other effects of long term LSD exposure far outweighs the mental benefits. It seems as if NZT(if it is real) would give that mental boost without the "tripping out" effect from LSD? Do you know of anyone...if it is possible...to make NZT? I would be interested in any info or guidance you may suggest.
Ralfy, there isn't enough wrong with you. That's the problem. Piracetam normalizes the brain's function and the more damage/aging the more the effects are shown immediately. When teens are given it and take a test a week or two later they score higher but virtually none will consciously notice a difference. They're mostly young and undamaged. Everyone will still benefit but because you're healthier than some (myself included), the effects will be more subtle and take longer to manifest. You can also try the other racetams - Oxiracetam is your next best bet for an immediate effect. Aniracetam and Pramiracetam cause sleepiness for most. Try them all if you can afford them. For Piracetam the manufacturer recommends taking it for at least two weeks before testing or noticing a difference. All racetams are long-term builders so don't panic when it isn't an 'instant pill' like the toxic, addictive caffeine/amphetamines/name-your-poison here. Piracetam is mostly about support. Taking it means not getting tired when you would otherwise. It's harder to notice not being tired than it is to notice being stimulated. The first is a lighter shadow; the second a brighter light. That isn't as noticeable as, say, the highly obvious and nasty effects of a stimulant. Effects that tell you in no uncertain terms that you've taken a drug. Piracetam just isn't like that because it doesn't unbalance the brain's functions like stimulants/sedatives/hynotics/psychedelics do. So you have to look at the shadows getting lighter more than the sunlight getting brighter - get what I mean? Your knight in shining armor is there but he's working in the dark so you can't yet easily see him. |
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Lo-Fi Version | Time is now: 20th April 2018 - 06:09 PM |