1565 replies to this topic

[Isochroma]

After making the animation I found OE to have received some new emails including two from Chinese chemcos asking for purchases.

So I wrote up a nice long email with pics asking about their custom synthesis or if they know of any other affordable Chinese custom synthesizers.

CS is just too pricey though when it can be bought from stock!

Molport: 1,4-dibenzoylpiperazine

Hell, why did it take until now for me to find Dirifiram's CAS#?

Feast your eyes on the prize: Google Image Search: 6091-41-4

And here is the perfect precedent: Dupracetam, whose full symmetricization corresponds to Dirifiram:

Dupracetam

Dirifiram

The Dupracetam molecule can be transformed into Dirifiram by expanding the N-N center bridge with the addition of four carbons to form the central Piperazine ring. It can then be seen that all the other components correspond to Dirifiram except Dupracetam's extra two Oxygens.

What's important to note here is that Dupraceam is just the symmetricized version of Piracetam. If it could retain nootropic activity then there is a very high likelyhood that Dirifiram will also be active.

If Dirifiram is also active, then I guarantee 100% that just like the subtle yet noticeable differences between Sunifiram and Unifiram reported on this forum, folks will also report that Dirifiram covers another area of the Nootropic Palette.

Edited by Isochroma-Reborn, 15 August 2013 - 04:01 AM.

[Climactic]

Nice work, Isochroma. I will note for the record that dibenzoyl is different from dibenzyl.

By the way, the user violetechos has kindly requested an unban if indeed you have such a ban in place.

[Racetams]

Hi,

These posts concerning new racetam like nootropics are extremely interesting. I would really like to see some of these made and become available.

Has anyone approached any suppliers to see if they can make it happen or fund it.

I was wondering if anyone could give me as much info as possible on them so i can start asking as many vendors and labs as possible so maybe we can get it made and sold.

I am sure someone will see the financial benefit and want to be first to market them.

Thanks

[Isochroma]

Wow, I had assumed the dibenzyl was a nasty stimulant but Wikipedia says no - wonder what it does.

Can't find a single forum report either.

violetechos is now unblocked.

Edited by Isochroma-Reborn, 15 August 2013 - 05:35 PM.

[golden1]

you cant just assume because something is symmetrical that it is going to be better or even active. that really isnt how drug design works... at all. : /

[Isochroma]

You're right!

That's why I use supporting evidence: Dupracetam.

You're still correct though: it's not possible to predict activity purely 100% perfectly on structures unless you can fully simulate them which we can't.

That's where the tasting comes in a la Shulgin.

[violetechos]

Mmmh the Sunifiram to Dirifiram gif is beautiful... I wonder if anything could be extrapolated from the SAR we know about sunifiram ...

I would like to see noopept (well its prodrug N-phenylacetyl-L-prolylglycine ethyl ester) symmetricized (I like this word... cyclicicized as well perhaps applies)

Cool work Isochroma!

[Isochroma]

Thanks! There's more today!

ISRIB

trans-N,N'-(cyclohexane-1,4-diyl)bis(2-(4-chlorophenoxy)acetamide)

Dirifiram

trans-1,4-Dibenzoylpiperazine

Today I by chancy luck found ISRIB - a molecule whose structure is merely an expansion of Dirifiram's.

I want to introduce ISRIB - a nootropic molecule that is the second besides Dupracetam to be both symmetric and nootropic. One of the major differences is that ISRIB's Nitrogens are exocyclic - outside the main ring. Ghelardini et al. found that exocyclization of both Sunifiram and Unifiram's Nitrogens reduced nootropic potency by some large amounts.

Nonetheless, this molecule shows nootropic activity and an excellent 8-hour half-life: "Subsequent testing found ISRIB to produce significant nootropic effects in mice, as measured by enhancement of spatial and fear-associated learning in standard water maze and conditioned environment tests." Note that the trans isomer was found to be nootropic. Sunifiram's skeleton is also heterostereoisomeric so it can be cis/trans and the Dirifiram produced from it by second-ring cyclization is also heterostereoisomeric - resulting in the creation of either cis-Dirifiram or trans-Dirifiram.

Only trans-Dirifiram is pictured here. I expect cis to be useless.

The four differences between ISRIB and Dirifiram are color-coded to the image's components. BLACK structure is shared.

1. ISRIB's Nitrogens are exocyclic the center ring.

2. ISRIB's Nitrogens are Hydrogenated to use up their unused bond after exocyclization.

3. ISRIB's dual benzene rings are joined to the core ring by ether linkages (-- O --) while Dirifiram's are directly attached.

4. ISRIB's dual benzene rings are para-Chlorinated but Dirifiram's are not.

These four are the only differences.

I predict with even higher confidence that Dirifiram will have nootropic activity.

Edited by Isochroma-Reborn, 17 August 2013 - 04:13 AM.

[violetechos]

ISRIB seems not completely stable... The Cl's on the end would be wiser to switch to F... . And can those oxygen bonds be doubled, the ether linkages don't LOOK too stable...Seems like metabolism could perhaps product some creepy by-products. I'm not 100% but from a cursory glance... No one knows until its bio-assayed yada yada :P

Difiram seriously needs to be made. There is magic in symmetry .

I see that CAD program in your head is working quite well LOL

Edited by violetechos, 17 August 2013 - 08:28 PM.

[Isochroma]

Indeed, I noted in bed last night that another shared feature exists between ISRIB and DM-232: the presence of a para-halogenated phenyl ring(s).

Quotes have been arriving for Dirifiram prices and they are pricey.

So my next project is to learn how to extend by 4 carbons and subsequently cyclize Sunifiram' propanoyl group. That's all that's needed to convert Sunifiram to Dirifiram. It may be a cheap single-pot kitchen-chemistry type of reaction.

Edited by Isochroma-Reborn, 17 August 2013 - 08:38 PM.

[Isochroma]

Just found an ISRIB group-buy thread on this forum.

[Isochroma]

Just found the ISRIB Group Buy thread on this forum.

As for the stability of ISRIB - the ether links [--O--] break first - they're notoriously weak.

Neither Sunifiram, Unifiram nor Dirifiram have these weak links.

[ThePhoeron]

Note: I've switched from cigarettes to e-cigarette---not only because of the recent discussion about not mixing tobacco with sunifiram on the side-effects thread, but that was certainly a big deciding factor. I found myself still craving "real" cigarettes over the course of the last two weeks as I've been getting used to the e-cig, so I've waited until I got over tobacco to start trialing sunifiram again, but this time with adrafinil and noopept. I didn't get any of the negative side-effects reported here from mixing sunifiram with caffeine or tobacco, but I figure I should minimize the risk factor when the neurochemistry is pretty clear.

Starting today, I'm trialing 300mg adrafinil, 25mg noopept, and 5mg sunifiram, taken orally in a gel capsule, 3x daily, four hours apart; I mainly want to see for my metabolism how many days in a row I can take this combo before developing tolerance. I've seen that the typical dosing of adrafinil is one day on, one day off, for one or two weeks a month, and that extended use of Adrafinil requires the taking of Milk Thistle. I'll be picking that up this week, since the liver is pretty damn important.

My first dose at 10am today kicked in after about 12 minutes---numb tongue, tingling in the cerebral cortex above the temporal lobes, and some feeling I can't quite describe but is somewhat like extreme self-awareness combined with minor brain-fog. The strange brain-fog like feeling lifted after about 20 minutes. The tingling in my brain stopped after about 5 minutes. The tip of my tongue is still numb after nearly an hour.

Adrafinil (and obviously the modafinil it is metabolized into) is definitely potentiated by sunifiram, and the stimulation is significantly above that of coffee, or sunifiram+noopept. I haven't ever tried Adderall or Ritalin, but the stimulation is significantly lower than crystal meth or cocaine, so it's not difficult to handle. It actually feels pretty smooth.

My unifiram and aniracetam should be arriving tomorrow, with any luck. The positive reports of combining unifiram with adrafinil and modafinil are good news. But so far, no negative side-effects from the morning dose, not even a little bit of anxiety---which is a big relief because this means I can actually make use of my noopept and sunifiram stash after all.

It's worth noting that I tried 300mg of adrafinil on its own, on August 15th at 6:30pm. I felt some stimulation and numb tongue for the first hour, but nothing much after that. At 10:00pm, I was already tired and went right to bed, which is really early for me. I slept great, woke up the next morning at 6am sharp feeling fine. I had vivid dreams, which is normal for me.

[jeftrit]

Please tell me if this may be harmful. After3 day washout I am going to encapsulate a synergistic mix. 25mg suni, 2g NALT 150mg caffeine and 8mg ephedrine sulfate. It should proove very stimulating. I will try this on empty stomach at 9am then repeat in 1hour with hot coffee.
any precautions I should prepare for at about 10:20 AM?

[Climactic]

Please tell me if this may be harmful. After3 day washout I am going to encapsulate a synergistic mix. 25mg suni, 2g NALT 150mg caffeine and 8mg ephedrine sulfate. It should proove very stimulating. I will try this on empty stomach at 9am then repeat in 1hour with hot coffee.
any precautions I should prepare for at about 10:20 AM?

NALT almost killed me after sunifiram, but it may be just me. I suspect it was due to too much potentiation. In general, I suggest you try NALT (with sunifiram) in multiples of 100mg only, and keep gabaergics + beta blockers including propranolol and atenolol on hand. Learn their dosages and chew them in the event your HR or BP elevates. Remember that BP elevation can be silent, but you can expect it to be correlated with HR in an event like this. If you choose to skip possessing the protective agents, then at least file your will and testament before you do it. Also, it may be better to try this in the Emergency Department's parking lot if not the waiting room.

Edited by Climactic, 26 August 2013 - 09:23 PM.

[jeftrit]

Thanks Climactic! Good advice as always. Will keep you apprised, my NALT order should arrive in 2d. Oh~ any idea where to get Neramexane? it may be the solution to the suni head pain syndrome. I only see it in a few clinical trials so far.

[Isochroma]

jeftrit: I'd stay away from the strong stims until you have plenty of Sunifiram experience under your belt.

Personally, I disrecommend and do not myself take any stimulants - especially caffeine and ephedrine - even alone.

Frankly, with the correct nootropic combination [and decently in-range sex-hormone levels] - such as Sunifiram and a strong racetam like Oxiracetam or Pramiracetam - no stimulants are needed.

[jeftrit]

Isochroma: I've been taking suni daily for 2 months now. What I thought was the often mentioned head pain due to taking too much of it may have saved my life. MRI was done; pain was not from suni but from a rarely diagnosed affliction from concussions. Seems TBI causes superficial siderosis. A little blood &(Fe) unleashed on an unprotected brain causes quite a bit of pain. Climactic knew my brain pain was different when I stated it was not present in temples but seemingly dead-center. Keep up the good work guys you are probably better diagnosticians and researchers than the local doctors. Thanx for all you do here.

[Isochroma]

Thanks for the report. Good to know that the headache was not from Sunifiram.

Free Iron is a very nasty prooxidant and likely quite lethal if present in high local concentrations near sensitive cells.

It belongs inside Hemoglobin and there only.

[Climactic]

Isochroma: I've been taking suni daily for 2 months now. What I thought was the often mentioned head pain due to taking too much of it may have saved my life. MRI was done; pain was not from suni but from a rarely diagnosed affliction from concussions. Seems TBI causes superficial siderosis. A little blood &(Fe) unleashed on an unprotected brain causes quite a bit of pain. Climactic knew my brain pain was different when I stated it was not present in temples but seemingly dead-center. Keep up the good work guys you are probably better diagnosticians and researchers than the local doctors. Thanx for all you do here.

Glad you could get an MRI. I might have to do this too. I am still not convinced about the positive connection you suggest from sunifiram, but in any case, you may wish to read the unifiram thread and consider it instead (if you haven't already).

Donating blood a few times a year is not a bad way to lose excess ferritin and also keep hemoglobin in check, assuming you otherwise qualify.

Meanwhile I suppose you can also look at general BBB-crossing ROS (reactive oxygen species) protectors. These overlap with excitotoxicity protectors, as excitotoxicity leads to ROS too.

[Isochroma]

jeftrit: Got your natural and synthetic solutions to get that iron out:

Deferoxamine therapy for intracerebral hemorrhage
Wikipedia: Deferoxamine

Nanoparticle and iron chelators as a potential novel Alzheimer therapy

Green tea catechins as brain-permeable, natural iron chelators-antioxidants for the treatment of neurodegenerative disorders

Tea flavonoids (catechins) have been reported to possess divalent metal chelating, antioxidant, and anti-inflammatory activities, to penetrate the brain barrier and to protect [against] neuronal death in a wide array of cellular and animal models of neurological diseases.

Edited by Isochroma-Reborn, 30 August 2013 - 11:07 PM.

[xsiv1]

A product called HM Detox also combines a variety of natural compounds in one formulation that may prove helpful.

[zongler007]

Does anybody try sunifiram in tablets from ebay ??? That new one (from uk) seller paying attetion at better quality then other supplieres but the price is higher, somebody have comparison ???

[8bitmore]

Does anybody try sunifiram in tablets from ebay ??? That new one (from uk) seller paying attetion at better quality then other supplieres but the price is higher, somebody have comparison ???

The general consensus on ebay for novel noots is: do not go there (unless you have extraordinary validation that they are legit (and no, ebay reviews does not count)). There has been a large number of flour packages sold if you catch my drift.

edit: also both your post and my reply belongs in the http://www.longecity...uct-discussion/ section more so than this thread.

Edited by 8bitmore, 12 September 2013 - 08:31 AM.

[FDA Approved]

I tried 5 mg of sunifiram (half a 10mg pill in the morning) and actually seemed to have positive effects (was feeling less cold outside, slightly less fatigued and in slightly better mood) however after fully reading this thread I have decided that it isn't worth it for me to experiment with it due to the risks. So if anyone wants 39 10 mg pills and lives in London (or wants to deal with shipping), I'd be willing to trade them for Piracetam or something else (feel free to PM me if you have anything to offer). The pills were both from here - http://www.intellime...nifiram-tablets .
I bought 40 for 28.50 + 3.95 shipping, however I would be willing to trade them for something of lesser value as I do not think that I want to take a 1% or whatever it is risk of doing something to myself.

[Climactic]

I tried 5 mg of sunifiram (half a 10mg pill in the morning) and actually seemed to have positive effects (was feeling less cold outside, slightly less fatigued and in slightly better mood) however after fully reading this thread I have decided that it isn't worth it for me to experiment with it due to the risks. So if anyone wants 39 10 mg pills and lives in London (or wants to deal with shipping), I'd be willing to trade them for Piracetam or something else (feel free to PM me if you have anything to offer). The pills were both from here - http://www.intellime...nifiram-tablets .
I bought 40 for 28.50 + 3.95 shipping, however I would be willing to trade them for something of lesser value as I do not think that I want to take a 1% or whatever it is risk of doing something to myself.

FYI - The email notification generated by your post above went to Junk Mail. I suspect this is because of your username. You may wish to experiment with a different one.

[Geoffrey]

I tried 5 mg of sunifiram (half a 10mg pill in the morning) and actually seemed to have positive effects (was feeling less cold outside, slightly less fatigued and in slightly better mood).

Yes, I would NOT recommend anyone to start off with a 10mg pill of sunifiram. For a newbie, the effects of that amount are quite noticeable. Even 5mg I found to be a strong, albeit pleasant, dose when I first started. Sunifiram seems to be cumulative (but I find all the -racetams to be cumulative and that they take a long time to wash out of my system, or at least their aftereffects take a long time to subside). I cannot now take more than 4-5mg, often every other day, with a washout period all weekend. Taking too much has a paradoxical effect on me. But this is also how I react to noopept, oxiracetam and (most recently) phenylpiracetam (which I found made me lethargic and drained at the recommended dose).

[violetechos]

Please tell me if this may be harmful. After3 day washout I am going to encapsulate a synergistic mix. 25mg suni, 2g NALT 150mg caffeine and 8mg ephedrine sulfate. It should proove very stimulating. I will try this on empty stomach at 9am then repeat in 1hour with hot coffee.
any precautions I should prepare for at about 10:20 AM?

NALT almost killed me after sunifiram, but it may be just me. I suspect it was due to too much potentiation. In general, I suggest you try NALT (with sunifiram) in multiples of 100mg only, and keep gabaergics + beta blockers including propranolol and atenolol on hand. Learn their dosages and chew them in the event your HR or BP elevates. Remember that BP elevation can be silent, but you can expect it to be correlated with HR in an event like this. If you choose to skip possessing the protective agents, then at least file your will and testament before you do it. Also, it may be better to try this in the Emergency Department's parking lot if not the waiting room.

Isn't NALT terrible? I don't like what it does to my head. Anxiety.

[Climactic]

Please tell me if this may be harmful. After3 day washout I am going to encapsulate a synergistic mix. 25mg suni, 2g NALT 150mg caffeine and 8mg ephedrine sulfate. It should proove very stimulating. I will try this on empty stomach at 9am then repeat in 1hour with hot coffee.
any precautions I should prepare for at about 10:20 AM?

NALT almost killed me after sunifiram, but it may be just me. I suspect it was due to too much potentiation. In general, I suggest you try NALT (with sunifiram) in multiples of 100mg only, and keep gabaergics + beta blockers including propranolol and atenolol on hand. Learn their dosages and chew them in the event your HR or BP elevates. Remember that BP elevation can be silent, but you can expect it to be correlated with HR in an event like this. If you choose to skip possessing the protective agents, then at least file your will and testament before you do it. Also, it may be better to try this in the Emergency Department's parking lot if not the waiting room.

Isn't NALT terrible? I don't like what it does to my head. Anxiety.

I always loved NALT before my incident with sunifiram. NALT was the fastest way to renew depleted neurotransmitters, with two slower ways being L-tyrosine and L-phenylalanine. With a 300 mg capsule dose, it put me in a great mood and worked as a stimulant too. If I used it too much, I became entirely tolerant to it, temporarily. It is powerful stuff.

I do wonder how NALT could lead to anxiety in some...

[protoject]

Closer examination of the study reveals that Sunifiram restores pulse depth by about 90% but at the cost of reduced pulse speed [lower frequency].

What exactly are the implications of this?

Edited by protoject, 01 October 2013 - 11:07 PM.