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Sunifiram (DM235), structurally novel AMPAkine

yaesutom

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I got some sunifiram about a week ago, and once again... disappointed :(

Piracetam is one of the few that actually has an effect on me - but just color perception, nothing "useful". I noticed a slight buzz when I first took ~10mg Sunifiram, but nothing since up to 30mg. Last year I got some Noopept from two different sources, and only noticed color enhancement when I took like 500mg at once (literally).

Maybe I should just eat the whole vial? lol.. I think people over-rate these nootropics.
 

Limpet_Chicken

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I would NOT reccommend it. I now plan to buy a little seeing as its commercially available before I clean up all that fucking piperazine.

Although I'd be surprised if you rated any of those proglutamatergic types, given your opinion of racetams and general love for ket.

That said, I find pramiracetam handy, but am just about the world's worst dissociative pig.
 

polarbearsarecool

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Yeah I also considered that exact combination. On the sunifiram thread at longecity there's people stacking it with all sorts of neuroprotective stuff (dha, citicoline, magnesium l-threonate, theanine).

On the topic of NMDA antagonists in conjunction with sunifiram, Isochroma experimented a bit with methoxetamine and found that sunifiram completely blocked any dissociative effect or cognitive impairment from 80 mg MXE taken without tolerance, but still produced a dramatic delayed afterglow "reset" type effect. There's speculation that a course of an NDMA antagonist may be the proper cure for those people who have suffered persisting neurological problems after sunifiram exposure (this is a problem that seems to arise when sunifiram is taken with stimulant-type nootropics such as phenylpiracetam or modafinil, or with other strong stimulants). So memantine may be a good prophylactic measure to keep sunifiram tolerance at bay and prevent undesirable neurological changes.

One very interesting point that Isochroma made, after his experience with the methoxetamine, is that with nootropics as strong as sunifiram, it is possible that they may strongly block the effects of general anesthesia used in hospitals. So what if someone needs emergency surgery, but they cannot be knocked out due to ampakines in their brain? :/

Regardless, I think it's fascinating how the nootropic technology is advancing like this. Coluracetam should be a good one, I have high hopes that it will be more sustainable/tolerable than sunifiram.

Isochroma.. is an interesting comrade.. but his underlying problems and somewhat overzealous combinations can put many in misconception land

Please note that for most typical general anesthesia operations they use ketamine in combination with propanolol which is a non selective beta blocker. Propanolol itself is very strong when used as a general anesthetic and is enough for the majority of patients.

The contrast of this is when I had surgery I was given JUST ketamine, no propanolol and I was on sunifram and provigil, many must realize that administered anesthetic levels of drugs are higher dosages in general, as well as the concentration (considered typical anesthesia) achieved for this scenario is MUCH higher than doing ketamine itself. The outcome being the ketamine overpowering the sunifram/modafinil and me coming out of anesthesia very quickly(within 5 minutes to an elevated baseline)

TLDR: NMDA and friends are NOT the only systems involved in cognition-but do not be afraid of these "racerams", and do NOT dose that high, 100mg sunifram daily is ABSURD. But keep in mind ampakines/racetams/racerams will not stop you from having anesthesia.
 

Limpet_Chicken

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Propranolol is a beta blocker, not an anaesthetic, general or otherwise.


Your thinking of propofol, the GABAergic drug. White milky solution, insanely fast but relatively short onset. Will knock the stuffing out of a bull elephant given a sufficient dose I'd think.
 

thickskin

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Jul 19, 2009
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Sunifiram is for me the most usefull racetam I have tried (tried ani, oxi, and noopept). At 10mg SL it gives me energy, focus, and a mood lift.

Only side effect I have noticed is a very light headache the first couple of times used (which I find with all nootropics)

It needs to be cycled as it does seem to have diminishing effects if taken daily.
 

Incunabula

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According to wikipedia:

Sunifiram.......enhances LTP in a bell-shaped dose–response relationship. This enhancement by sunifiram is associated with an increase in phosphorylation of AMPAR through activation of protein kinase II (CaMKII) and an increase in phosphorylation of NMDAR through activation of protein kinase C α (PKCα). More specifically, sunifiram stimulates the glycine-binding site of NMDAR with concomitant PKCα activation through Src kinase. Enhancement of PKCα activity triggers hippocampal LTP through CaMKII activation.[8]

And about which it is said:

Increased activation of PKCα is associated with the growth and invasion of cancers.[12][13] High levels of PKCα are linked to malignant brain cancer.[14] Moreover, a high proliferation rate of glioma tumor cells is the result of overexpression of isozyme PKCα.

Does this mean Sunifiram increase the risk of brain cancer? Sounds like it.
 

thickskin

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Does anyone know anything more about the cancer link? I won't be taking any more until I can find out more about this
 

Limpet_Chicken

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Sunifiram is not a racetam, thickskin. It is a diacylated piperazine, rather than a pyrrolidinone derivative.
 

tweex

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On the tweek again. Drinkin' county prune!
Does anyone know anything more about the cancer link? I won't be taking any more until I can find out more about this

Totally overblown. This is precisely the same phenomenon at play that this site mocks: http://www.dhmo.org/cancer.html

Just because PKC-alpha is a signaling enzyme in cancer cells doesn't mean taking a drug that activates it will give you cancer.

No different than saying "water is in cancer cells so water gives you cancer"
 
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hollywood_cole

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Nov 16, 2008
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re: the PKCα thing: would it speed up tumor growth if the cancer cells were already present?

would this risk be present with aniracetam?

and piracetam is considered to be fairly safe and has been used without serious problems by many people for many years (decades?), correct?
 

tweex

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On the tweek again. Drinkin' county prune!
As to your first question, I'd say that much is at least plausible. But frankly if you've already got any variety of high grade astrocytoma, you are proper fucked in the long term regardless of how many resources you throw at the problem. http://www.ncbi.nlm.nih.gov/pubmed/18508315 The fortunate part is they are also exceedingly rare, I believe your odds average out to about 1 in a million in a given month, but much higher for a tall middle aged man.

To my knowledge, aniracetam only activates gamma-PKC. It is however interesting to note that administering several different nootropics leads to later PKC downregulation http://www.ncbi.nlm.nih.gov/pubmed/8246681

And you are quite correct on the safety profile of piracetam. I've personally consumed kilograms of it, and have nothing but positives to say about it, aside from the terrible taste and high effective dose (easily solved with a vaporizer or some 000 caps)

Edit: also interesting to note Sunifiram appears to be based off BZP

BZP:
500px-Benzylpiperazine.svg.png


Sunifiram:
Sunifiram.png
 
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dopamimetic

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This made me really curious. I have had bad reactions to the racetams I've tried (mostly Aniracetam- got tensious, anxious, nervous, depressed...) but also Piracetam itself, Pramiracetam I don't remember but it was not impressive at all, or I would remember more if it :) Also the fact that I do react very positive to NMDA antagonists, be it dissociatives at sub-psychotropic dosages or that Memantine I'm taking currently, let me wonder about all that Glutamate stuff and its different receptors.. that for myself NMDA agonism / sensitization probably is a bad thing (after the initial brain fog lifted, cognitive capabilities are at least comparable to soberity, the calmness that NMDA antagonists give me induce the ability to think more before reacting, helping much in keeping anger / aggressive impulses down..)

But so this one could be the next candidate to try, given it's a selective AMPAkine (or combined with continuing my Memantine to cancel possible effects on NMDA receptors)... A sample order is on it's way, will see how it behaves...
 

Repulse

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Feb 26, 2008
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This made me really curious. I have had bad reactions to the racetams I've tried (mostly Aniracetam- got tensious, anxious, nervous, depressed...) but also Piracetam itself, Pramiracetam I don't remember but it was not impressive at all, or I would remember more if it :) Also the fact that I do react very positive to NMDA antagonists, be it dissociatives at sub-psychotropic dosages or that Memantine I'm taking currently, let me wonder about all that Glutamate stuff and its different receptors.. that for myself NMDA agonism / sensitization probably is a bad thing (after the initial brain fog lifted, cognitive capabilities are at least comparable to soberity, the calmness that NMDA antagonists give me induce the ability to think more before reacting, helping much in keeping anger / aggressive impulses down..)

But so this one could be the next candidate to try, given it's a selective AMPAkine (or combined with continuing my Memantine to cancel possible effects on NMDA receptors)... A sample order is on it's way, will see how it behaves...

I'm currently taking 5-10 mg on a daily basis since tuesday. I stack it with 250-500 mg Choline Bitratate and Sulbutiamine 300 mg and multi-vitamins as well as Omega 3-6-9 fish oil with high contents of EHA/DHA.
So far, so good. I feel more motivated, focused and the extra source of Choline i'm taking (the bitratate) seems to prevent the headaches.
 

suni_hatamoto

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Oct 3, 2020
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Supplying my experience here, too, since it's a harm-reduction forum, and I, uh, got plenty of harm from this substance. Though recovered in the end.
(Sorry if I'm doing "archeology", I believe there's no need to spawn separate thread for this.)

SUNIFIRAM TOXICITY REPORT (ALSO - MITIGATION PROCEDURES)

Used Sunifiram for 6 months straight every day, once per day, sublingual, 5-15 mg eyeballed with very small scoop.
First month it felt like quite an improvement, but after 2 months it started to give a burning sensation in my brain (felt like I had a bunch of mustard plasters inside, i.e. "burning" like a spicy thing does it).
The sensation disappeared after discontinuation.
After some time I've took 50mg of L-Theanine sublingually, and was immediately blasted again with a hot burn, of the whole brain (at least it felt like that), for 2 days straight. It subsided afterwards, but felt extremely unpleasant.
The burning pain didn't disappear completely this time, and has started to show itself during mental work.

A bit of time passed. I've, obviously, made a mistake again, now with memantine. I've self-medicated with it (5mg per day) for 2 months (last month I've took it sublingually which, for memantine, significantly changes its MoA since it targets many receptors and has many metabolites to do its work).
This broke my sleep, and I've acquired even more serious headache that started to appear during any learning process, listening to music, computer games, any media other than a something like a light novel.

I've visited a sleep specialist, but nothing worked (got a brain scan, it was alright). At this moment I took his suggestion and went to a shrink. Got diagnosed with "moderate depression" (but I didn't understand the diagnosis since I was able to work; later it turned out that I've pushed it all along by sheer force of my stupidity, as I did it when I've been taking sunifiram, paying no attention to burning pain or the fact that it was an untested drug). It also became clear that the depression was: chronic, slowly accumulated over my life, was present since childhood (about 6 years, death thoughts came around 8 years and became a habit of mine, I mean the thoughts, not the actual decision or intention to follow through).
The initial round of antidepressant+sleep-med combo worked alright, but only reduced my depression to a "light" level. The sleep improved after than 1-month course, though (the med was named Truxal, the SSRI - Cipralex).

Then we discussed and went through with Paroxetine (to try to treat anxiety issues).
Boy, that was a wrong move.

After a month of Paroxetine I've got that burning pain all over my head, but now it was constant (!), like it never, ever stopped (6 out of 10 sometimes, but mostly 4, if you want a pain rate). The only good thing was that I was able to fall asleep and actually sleep. (I also was able to work, again, by sheer force of my stubbornness and obstinacy. Only later I uncovered that other people can't stand even a 3/10 for a few hours, lest be it a constant pain.)
I've weeded off Paroxetine during 4-month period, but now was stuck with lesser form, but still present, of chronic depression and, more importantly, constant burning sensation in my brain.

Then, when any pain-specializing doctor that I've gone to said that he is unable to help, I've compiled a list of possible medication and combinations to try and presented them to my shrink. Turns out, he had a bit of experience with pain management (since people with psychiatric issues also do have somewhat strange types of pain), so he reviewed it and crossed off some irrelevant things out.
I've followed through the medications for following 2 years, and no thing or combo (even exotic ones) did work. I won't write what didn't work here, but I'll say the meds were mostly for fibromyalgia (SNRI, anticonvulsants, tried some antipsychotics, etc.).
Nothing worked until we've came to pregabaline and phenibut.
I honestly don't know why no neurology specialist has recommended this medication to me, since it was the only thing that worked. But, there's always a catch.

To heal, I had to follow this schedule: 150 mg pregabaline, 2 times per day (morning/at night), for 28 days. Then 2-3 weeks off the med (say hi to withdrawals). Then see, if symptoms improved. Continue until the first week of pregabaline will start to result in extreme sedation. If so, stop the med, rest for 2-3 weeks, and attempt to repeat, now, with 75 mg of pregabaline (in same way). If extreme sedation appears again, go off the med, and try to finish with course of phenibut (for 10 days straight, around 500 or 1000mg max per day, in same way).

I've put with it for a year and few months. After a week of the med, the pain only increased, about 1.5-2 times more. All this time I was working, as a software developer, so I had to bear through the pain every working day. And during withdrawal it increased even more.
Still, I had nowhere to run, so I tried to muddle through with everything that I had.

At the end came the time when the pain disappeared almost completely (I'll go with a last round of phenibut some day, I guess). At that time I also started to get other side effects from the med, i.e. skin on my head started itching severely. So I stopped at 14th day, and didn't continue anymore. I didn't have the need, though, since the pain (compared to what I felt during 6-month sunifiram course) has disappeared. I suppose the itching will disappear at some time, too, I will deal with it somehow anyway (antihistamines didn't work for it, so it's not an allergy?).
I still can't use any coffee, though, after all that experience. Obviously alcohol is a no-go for me (it doesn't even work on me as it should, the effect disappears very quickly).

Reflecting now, I see how foolish my decision were, to play with something more powerful than a choline supplement or caffeine drink. I should've shown more grit instead (and directed my stubborness into that) of focusing on "easy way" through "magical" substances.
I understand that my account is new, but I hope the system will allow this message to stay for a long time, and won't suddenly remove it from this site.

I also understand completely that there are people who didn't had any trouble like this, be it Sunifiram, Unifiram or anything else. The point is, I've took these subtances for a long period. And the thing that exacerbated the symptoms of pain were none other than Memantine and SSRI/SNRI. So while people will point out that they had no such issues with AMPAkines, I want to remind that these are LTP potentiating agents, sunifiram, for example, stimulates PKCα pathways (cancer cells much?), - there's no good reason to take these substances if such side effects do occur. And that you should probably be careful with (at least) sublingual memantine, but this suggestion is built solely around my experience.
The other argument is that I had chronic depression and that probably other people won't have these "burning" side effects. Well, I remember messages from people that they actually got these "burns" from Sunifiram, too, with no indications of having clinical depression.

Thus:
Do not use Sunifiram or Unifiram, hoping this will magically escalate your thinking abilities, period. (I suppose this also goes for any really strong AMPAkine, like nefiracetam, fasoracetam, etc; Sunifiram is not an AMPAkine, though it somehow works on AMPAr.)
Do not *ever* use Sunifiram or Unifiram for longer than 30 days, and don't *ever* use AMPAkines if you have glutamate issues (like epilepsy?).
Do not use or be very careful with L-Theanine and Memantine after you've (again, don't do this) been through long enough course of Sunifiram (so it started to burn).
Do not combine strong AMPAkines/Sunifiram/Unifiram with stims.
As anecdote: "VERY strongly contraindicated, beta-carbolines and DM-232 and DM-235. Seems to agonise purkinje cells, a GABA mediated receptor in the cerebellum.", and another: "Don't take sunifiram with butylone, or modafinil, or adderall (separate pairs)".
And of course, I strongly recommend to not use any substances that were not properly tested on volunteers.

Personally I've came to believe that most people don't need most of the nootropics other than citicoline or something like that (after they turn the page, say, around 25 years). What they need is good external toolkit (computer, writing tools, proper software), and access to real, good education (be it specialists or facilities). Also, if you're interested in logic and thinking, then you probably should try a bit of classical philosophy, and Wittgenstein for contrast, and throw in some great psychology book like "Psychology Applied to Modern Life: Adjustment in the 21st Century" and "Core Concepts in Classical Psychoanalysis" (Morris Eagle).

Also, I've tried many nootropics before (and including) Sunifiram. The point is that I was studying at university during that time, and what is really funny, is that, of all things, Sunifiram seemed to be the most effective and most devastating to me; citicoline being the second in terms of appeared effectiveness (I do believe most people do appraise changes from noots subjectively and not with proper RCT experiments, nor did I).
Note that changes brought with this regimen of Sunifiram use are now irreversible. I've reduced the pain significantly, but only that much, it won't revert to pre-Sunifiram anymore (also because I won't be able to bear through side-effects of Lyrica further; nor that pain reduction definitely means "reversal of Sunifiram-caused changes"). It very well may be that even a month of Sunifiram can bring some irreversible brain changes, do be cautious with that.

(Fortunately, the year on Lyrica, and a bunch of clever psychoanalytic techniques and conversations, too, mostly cured my depression. At least I can't say anymore that I have it (no bad thoughts too). Lyrica also seemed to cure my IBS that I was struggling with since god knows when. So "overall" it has been a "success" (sarcastic one); don't worry, things are going well for me now.)

Finally, during that period I've also got a message that said the guy had similar burning pains due to Effexor (after times of drug abuse; alcohol made him paranoid).
That made me think that same "burning headache" may appear from other drugs, in completely different way, and that a course of Lyrica probably may help people with issues like these. The difficult thing is to persuade your doctor to help, though (and insurance, how could I forget insurance?), and to follow with the treatment (especially when nasty side effects start to appear).

Be safe.
 
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