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N&PD Moderators: Skorpio
Ampakines: any experience?
- Thread starter Huntley
- Start date
23536
Bluelight Crew
many ampakines are poisons
I too am curious about reports of ampakine use. This has been asked before, but (so far as I know) no response has been given.
perKeceT
Bluelighter
are these relatives of amphetamines? and as far as i know the information regarding your source shouldnt be included in your post. sorry i have no pertinent info for you though, honestly most of ADD goes right over my head, but im trying to learn what the people here talk about!
23536
Bluelight Crew
an ampakine is a ligand of the AMPA receptorThe mechanism of action- as far as it's known- is entirely unlike your typical garden variety substituted phenethylamine sort of stimulant.
Potential seems vast, and yet I can't find any experience reports on it.
Anyways, I will be ordering an overseas shipment next week regardless, maybe I can be the first to report my experiences with CX 546
ebola?
Bluelight Crew
The evidence is not clear: though far less dangerous than NMDA agonists (positive allosteric modulators), we can't assume a lack of potential neurotoxicity. That said, this is a novel arena, to be filled in soon. That said, this class of agents holds a lot of promise.
ebola
DJHENRU
Bluelighter
are you talking about non recetam ampakines?
Edit:derp
23536
Bluelight Crew
oh, if he's talking about racetams I lost most of my interest.
piracetam is invigorating but it's no magic bullet. Also, I tried pramiracetam and got zero effect, which makes me think it's active at much higher doses than 300 mg. With pramiracetam I bought the tablets, but with piracetam I bought the half-kilo bucket and was able to ad-lib the dose.
There was a bluelighter who was assaying sunifiram, but I don't think he reported on it.
There are so many nootopics more potent, looks damn impressive, what ppl forget as that those study's talk about more potent by weight, eg you need a smaller dose to achieve the same effects, this does not mean at all that higher doses will achieve better results then the lower doses.
The racetams have no evidence behind them in healthy human subjects either.Limpet_Chicken
Bluelighter
Said bluelighter with the sunifiram project is me.
I have the piperazine, the propionyl and benzoyl chlorides.
However my fuckup former housemare, when I booted her out of my house, got some revenge by claiming I was committing some serious crimes, which I was not, and am not committing, the filth kicked my door in at 7am, killed 100s of my pet spiders, just newborn babies no bigger than pinheads, took my glassware, almost all of it, and some chemicals I would have been using. The glassware will be returned, as the bacon cannot find evidence of any crime from it, as there has been no such activity, but whilst the case is being investigated by the incompetent, in some cases lying, fucks that call themselves forensic chemists
It WILL be done, and soon, I have a new set of glassware, but I need to get a vacuum pump for fractional distillation, and TLC plates to confirm both the success of synthesis and the purity of the finished sunifiram, and some appropriate solvents, as I currently lack a polar, aprotic solvent in which to dissolve a monohydrochloride salt of the piperazine, can't use anything like a ketone, alcohol etc, as that will eat up the acid halides faster than you can say 'waste of expensive reagents'
One other thing stopping me, has been my cognitive and memory impairments themselves, until very recently, after using methoxetamine for a week or so (a gram in total) my thought processing, memory, attention span and motivation has been so badly impaired that a day that I am functional and able to do the daily activities I wish to do, or even sometimes cook a meal that involves any more complicated work than 'stick in microwave, and press the button, then eat', or 'stick in oven, set timer, take out and eat'
And also, I recently obtained a 100mg sample of desoxypipradrol, and the functional improvement in my life...even after the huge improvement from the MXE use, post-period of use, is again very much better, 0.5mg/d to 2.3-3mg every other day, early upon wakeing, with no side effects, barely perceptible, does not impair sleep or appetite...I have recently become so much more able to function day to day, although the improvement in specifically mnemonic abilities is not so pronounced, not enough, but combined, the works, makes me much more able to achieve a good performance when the sunifiram is produced.
Money has been a factor also, I have no job, not for want of trying, indeed I have been doing so since I left school at 16, I am now 24, and without exception, every single business or person I have asked for, indeed sometimes begged for just the chance to prove myself as a hard-working, honest employee, I get turned down. Its always 'no experience, go away', or we are full and no work is there to be had, and my sole income is due to both being classically autistic, and being disabled (knee is buggered, difficult to walk, constant pain, muscle weakness in the affected leg. I mind you, do not consider being autie as a disability, indeed, I HATE the fact have been born without, or to be 'cured', life as I know it, for me personally, would be less worth living)
My income, until recently, was a mere pittance, sometimes I couldn't even afford a meal, save for the scraps of my parent's meals occasionally given, and scraps of crappy food around the house, and had to save for weeks for a single reagent at times, months and months for decent glassware)
No experience, sorry, we don't want you (one job app I actually managed to get an interview for, bar work pulling pints), said no experience needed, training will be given, had the interview, was polite, well dressed etc, was willing to work my arse off, and after that, the guy actually said, right after to me, sorry, changed my mind, you have to have bar work experience afterall. And the longer I have no work experience, the harder it gets (''why don't you have any work experience? there is probably something iffy with you because of that, etc.'' If I never get given a chance, how the fuck am I meant to get any experience?
I will report on the effects when the project is complete though, definately. As far as I am aware, there are no public bioassays at all for the compound in question.
And as for effects in healthy subjects, I am not one of those, regrettably, piracetam did help, aniracetam was far better, I need to buy more of the latter, and when I tried galantamine, just for a short time, a little over a month, almost a month and a half, it was life-changing. Sadly, it is, for the forseeable future, the ONLY time I will get to try it, as it is horrendously expensive to buy, and here in the UK, it is IMPOSSIBLE to get it prescribed, it is only given to patients with dementia, or alzheimer's, and even then, only to some of them, and only in advanced alzheimer's patients, even then, only some of them are lucky enough to be given the chance for a short period more of what can be called a life, rather than a tortured, degrading and ultimately fatal mere existence.
For people like me, young, but with non-dementia, yet severe functional impairment of memory, there is no help that will be given, they will willingly do memory function tests, and retest, retest again, and yet again, but then discharge you, and you are left to suffer, I have pleaded with so many doctors and specialists, not for months, but years, and not a finger has been lifted to actually help me.
Every single thing that has been done to help, has been done at my own hand, at my own, ill afforded personal expense.
And you know what, that fucking sucks, and both saddens, and angers me, the current state of affairs for cognitive impairment, aside from perhaps that caused by a poorly functioning thyroid, which of course is easily treatable and reversible by everyday, available and common as bloody much thyroxine replacement therapy, is that there is simply nothing to be given. Memantine is used in this country, as are several cholinesterase inhibitors, but will you get them? you have as much chance of getting either, as of walking into a pharmacy and politely asking if they will give you a kilo of morphine for free.
The AMPAkines are much more selective for the learning process in the initial stages of encoding, and and strengthening neuronal connections, via induction of LTP, than are the racetams, and in addition, some of them also inhibit desensitization of the AMPAr (which with glutamate as the binding ligand is very rapid indeed) prolonging, as well as potentiating glutamate-induced ion currents, and most of them also release BDNF, which is both neuroprotective, antidepressant and induced neuroproliferation, survival and differentiation, although its action is very complex, depending on how, where and possibly when it is released, and can actually have antagonistic effects upon the alpha7 nicotinic AChR in some cases, whereas agonists of A7 nAChR are nootropic (indeed galantamine does so, in addition to cholinesterase inhibition, and I found it MUCH more effective than was huperzine-A, which did however help me, and is far far cheaper)
Glutamate excitotoxicity wise, AMPAkines are allosteric positive modulators at AMPARs, and act to potentiate bound glutamate (off topic, but quick Q: Do AMPA receptors also have aspartate as a native ligand, as do NMDARs?) an allosteric modulator does NOT activate (or decrease the activity of it, in the case of a negative allosteric modulator) its receptor in the absence of an orthosteric agonist does bugger all) Excess glutamate, or an exogenous ionotropic glutamate receptor agonist at the glutamate binding site IS neurotoxic, as evinced by GHBr agonists which release glutamate, or such direct agonists such as domoic acid, kainate, AMPA, quisqualic acid, and NMDA itself KILL cells, by flooding them with calcium ions, and are used in lab animals to cause selective lesions to parts of the brain exposed, for studying impairments to that section of the nervous system or brain structure, if microinjected locally into the brain, or if given systemically, they act all over the show to cause seizures, and permanent damage both structurally and behaviourally.
A naturally occuring example is domoic acid, which sometimes accumulates in shellfish, through their ingestion of plankton blooms which produce the substance, and in certain types of algae. This causes a syndrome called amnesic shellfish poisoning in the human when said creatures are eaten, symptoms are, aside from gastrointestinal issues, selective destruction or severe damage to the hippocampus, a brain structure critical for formation of short term memories and working memory, and subsequent transfer to longterm memory via LTP, as well as epileptic type seizures. This can cause permanent inability or great deficit in mnemonic function via excitotoxicity, as well as prefrontal cortical damage.
Some AMPAkines, but not all, depending on the aminoacid residue at the Q/R editing site, and flip/flop type isoform of the AMPAr structural composition, are calcium-permeable AMPAr selective, and some are not, and some prolong the duration/and/or amplitude of the ion flux on glutamate-induced channel opening and some inhibit the desensitization of the receptor as stated, and probably some do both. Ones selectively inhibiting AMPAr desensitization (enabling glutamate to stimulate the receptor and allow the neuron to fire off its action potential again quicker than normal) are, I believe, less likely to enhance neurotoxicity in cases of excessive glutamate concentrations (which in normal healthy brains are very rapidly removed indeed) I do not believe, due to the nature of enhancement, rather than direct stimulation of AMPARs, are at all likely to be neurotoxic, and they appear to be quite safe in lab animals.
Aniracetam is an AMPAkine, to a degree, and AFAIK piracetam has been found to bind as a positive modulator to an allosteric binding site for positive modulators (of which binding site types there are several known) and both drugs have a track record of being very safe indeed)
I can't wait to try sunifiram out.Last edited:
23536
Bluelight Crew
^ acylpiperazines I have known and loved.
interesting
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Okay, don't take the wrong way but:
Reading over your post, there's no way you have "severe functional impairment of memory." You're able to write a coherent, logical post of over 1500 words and in it, demonstrate solid knowledge of chemistry, pharmacology, and neurobiology. I don't doubt that you may have some psychiatric problems, but your cognitive abilities seem to be functioning quite well. If you really had such a memory deficit, I doubt you'd be able to remember what an AMPA receptor was, much less its significance in long-term potentiation.I had some CX-516 custom synthesized a few years ago. The stuff didn't look very pure. The color was brownish (which might well be normal, I'm not sure it's supposed to be white). The smell was awful (if the container wasn't airtight it would smell in the whole room). I tried it a few times (up to 200 mg). It make me feel dizzy and I feel some kind of "pressure" in the head for about 30 minutes. The stuff is very acidic and upset the stomach. CX516 is known to upset the stomach but I don't know if it's for the same reason. That's the main reason that I don't want to try it again. I have a very sensitive stomach and don't want to take too much risk.
narco anonomous
Bluelighter
- Joined
- Mar 2, 2006
- Messages
- 229
Ziddy, you seem to be applying a different criteria to memory than would a pathologist. For starters this is done over the internet, where a vast sea of information is at the finger tips. The memory maybe implicit, when you see it you know it, but I imagine what he is describing is declarative or explicit memory (ability to recall facts, names, etc). Personally I have a form of autism where my interests are restricted. Some things and subjects I remember, somethings I forget. It's a pity the brain isn't better at translating memory in typical humans, but at the same time would you really want to not have the ability to forget things? I digress.
nuke
Bluelighter
- Joined
- Nov 7, 2004
- Messages
- 4,190
That might explain the post length...Limpet_Chicken
Bluelighter
Bwahahaha Nuke, indeed, got it in one, although it was a combination of said piperidine and a solid dose of dihydrocodeine.
That was the night I cautiously took it up to 5mg, which was too much for me personally, no overstimulation, just too long lived, don't think it was really the long life or potency that bothered me really, just too much of a drain on my arsenal of sedating and anaesthetizing agents when I decided to get some sleep, two weeks worth of a nitrazepam (5mg tabs) in a single dose, plus 20mg temazepam and a shot of vodka, and I couldn't even notice I had taken them, and on top of that, to finally put me out, it took repeated plugged doses of up to 10mg per, sometimes more, of tizanidine.
To contrast, 4mg of the latter administered that way, would have me out cold within 10-15 minutes.
Memory impairment wise, its often the case where if I have two seperate tabs open on my browser, and have to remember a few words, or a serial number for a program, I can't remember more than 3-4 numbers at a time, or a couple of words, or I preheat the oven to make a meal, and then go for a fag, and end up going off and doing (or trying to do) whatever, and come back hours later, thinking 'fuck am I ever hungry' only to find a defrosted meal on the kitchen counter, the cat warming himself on the top of the grill and the oven, empty, busily burning away.
So there is a quite definite working memory deficit, and transference to longterm memory is also impaired. I have been reading, and re-reading the same huge wad of research journal printouts on ergot biology for over a year, and I can still only partially recall what I have learned. My intelligence is not impaired, but ability to process and concentrate is, and my executive function is shot to shit.
Cognition is more than just intelligence, not to boast, but I do consider myself to be of reasonably good intelligence, there is just so much more to it than simple smarts. I would define it as the entire sum of intellectual function, AND the actual, practical application of it.
I have a good reason (in my opinion) to suspect that my issues, are at least in part, due to glutamatergic excitotoxicity, I have had several really nasty run-ins with GBL dependence, which has been known in low doses, to be excitotoxic (actually it is activation of the GHBr, but by all accounts, GBL use=GHB use) and also, once, a far, far FAR worse experience being physically dependent on barbs, used a shitload of veronal a few years back, and then got arrested, after ODing, and remanded. Barbs are AMPAr antagonists, although this antagonism is of a curious nature, locking glutamate in the receptor, whilst maintaining it in a desensitized state. Sudden removal of GABAergic inhibition, I.E sudden lack of the main inhibitory CNS neurotransmitter would render one more suceptible to excitotoxic damage if said process occured, would it not? and concurrent AMPAr stimulation due to a rebound from chronic antagonism sounds to me like it would greatly enhance any excitotoxic damage going on.
Do you think, people (nuke, I am especially interested, given your knowledge, in your input) that that alone, the continuous attatchment of glutamate to its receptor, trapped there, but whilst said receptor is desensitized, would in and of itself, irrespective of the barb withdrawal would be excitotoxic? can a desensitized receptor still trigger action potentials, albeit of lesser amplitude? and would this, in that rather unusual mode of antagonism, have the potential to cause repetitive, sustained channel opening?
Survived Abortion
Bluelighter
Limpet_Chicken
Bluelighter
Lol, that was a one-off.
Usually the moggie script gets put in a drawer and saved for if they ever really are needed, I had lost my patience waiting for the desoxy to wear off, whilst titrating the dose.
Normally, I use the nitrazepam once to twice in two weeks.
egor
Bluelighter
Anyone have more info on ampakine modulation of BDNF? I already have the articles on BDNF modulation from Drug Discovery, but any other sources would be appreciated.
