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Nootropics of the future

If we did get a selective orexin agonist it would probably be a mildly euphoric, appetite stimulating stim.
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How would we know whether it's mildly euphoric, especially when the downstream effects of the endogenous peptide have not yet been plotted out particularly clearly?

ebola
 
ebola? said:
How would we know whether it's mildly euphoric, especially when the downstream effects of the endogenous peptide have not yet been plotted out particularly clearly?

ebola
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Its been shown to be involved in both wakefulness and reward in animal studies, just a bit of conjecture on my part. Also from a buddy who trialed MK-4305 (nonselective antagonist) in an open label study, blocking orexin is depressing as hell.

http://en.wikipedia.org/wiki/MK-4305
http://www.sciencedirect.com/science/article/pii/S0166223606001731
 
hi guys i have a question for you, i was going to make a thread on it i could but i figured i'd just post here for some thoughts

what is required to be known or to happen for real smart drugs to happen?

I hear the phrase "hammer on a nail, instead of a scalpel" how does that apply to neuropharmacology?

from what i understand we will need to learn more about exact functions of the brain and specific areas for specific functions and more understanding on the more specific parts of what we want to tweak and their specific regulators, is that all?

what will need to happen in neuroscience for real impressive substances to emerge, what needs to be known?

from a linear eliminatory thought process what will need to happen to get nootropics of the future?
what are the obstacles in the way?
what technology is lacking?
what are the lingering unknowns?

and i am referring to all cognition enhancing pharmacology including psychstimulants etc

I was just thinking about this internally and think its very much worth getting further depth of thought on, at least it can add some substance for us here to think about.
 
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I thought I'd do a bit of dumping on 5HT6 antagonists (note that these are rat studies):
- Increase cholergenic and Glu transmission
- Increased memory and frontal lob function http://www.springerlink.com/content/tm322314mn376402/ http://www.sciencedirect.com/science/article/pii/S1074742711001262
- Antidepressant and anxiolytic effects http://www.springerlink.com/content/a6314mu834746382/
- Sedation in rats http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2225549/

Big ol' review and current trials:
http://www.sciencedirect.com/science/article/pii/S1933721308001001
 
Lombergerh said:
But have anybody tried something from AMPA-family?
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I wonder the same but also about pure dopamine agonists & DAT allosteric regulators; if the former treats neuro-degenerative disorders I'd think it wouldn't be outside reason to claim nootropic capabilities.

Few stimulant experienced users, I doubt, have been administered dopamine receptor agonists to rightly compare them to the subjective effects to those of non-receptor, DAT mediated, indirect agonists. Namely DRIs & DRAs.

Ampakines and glutamate mediated type nootropics would likely be less reinforcing than perhaps the quinazolinamine type DAT site binding drugs.

Drugs which cause DA upregulation and heightened expression might, with long regimens of use, work as nootropics as well.
 
Sorry for the bumping old thread, but does anybody have interesing/useful information about "peptid-nootropics", perfomance enhancers, or something new on this field.
Not include these russian nootropics like Semax or Selank, used them and really not get much of it.
I'm really interesting in some experimental drugs, that currently only under development or clinical trials
 
I'm glad someone bumped this thread. There seems to be less and less interest in nootropics. I'm quite interested in the potential benefits that Orexin agonists may have on cognitive performance or motivation... they're some years away yet though :(.


Nagelfar said:
Drugs which cause DA upregulation and heightened expression might, with long regimens of use, work as nootropics as well.
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Would CDP-Choline fit this description? I only became interested in it since I read this on wiki:
Cocaine dependence is associated with depleted dopamine levels in the central nervous system. In cocaine-dependent individuals citicoline increases brain dopamine levels and reduces cravings.[15] In the general population citicoline increases brain responses to food stimuli, specifically in the amygdala, insula, and lateral orbitofrontal cortex, which correlate with decreased appetite.[16]
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CDP-choline has removed my "need" to smoke weed to feel best off and best focused, it also in general makes me much more satisfied with how i feel(I feel a lot healthier and .. like life is smoother) so I am much less likely to crave any drugs really.. however I never kept it up for longer periods than a couple months but it worked every time. It certainly seems like it does something with dopamine.
 
Sort of bump here, i recently obtained Metaprote(Ethylthiobenzymidazol hydrobromide) it's relatively uncommon on the usa market and i would appreciate any interesting info about this substance.
All that i could find it's "playing" directly with your cells, RNA synthesis, and something else.
 
I couldn't find much for it in English, mind posting some literature?
Been drunk since my MCAT =D
36 on AAMC 10 :D
 
It helps to search for ethylthiobenzimidazole. Still, I don't see much english research.
 
I see racetams and ampakines already mentioned. I still seek qualitative data on the effects of the ampakines. However, I can say that noopept posesses the greatest potential of all the racetams. Taking it with choline greatly reduces side effects and potentiates nootropic activity. Additionally, I find the racetams to posess interesting desensitization properties as doseage increases. No need exists to take Noopept in a dose between 10 and 50 mg. A few mg's will provide the most consistent benefits. Analogously, I find 800-1600mg the best dose of piracetam. Higher doses tend to impair memory and focus while enhancing others such as emotional sensitivity and visual pattern recognition. Fortunately, it has a high LD50/threshold_dose ratio, so one can use high doses recreationally. However, I feel that 'more' does not equate to 'better', and prefer 5 mg twice daily. I also recommend a tolerance break over weekends to consistently maintain nootropic activity.

As for the overall effects, I find them more salient than those of the subtle piracetam, though I find Noopept significantly less stimulating. I consider this a positive effect. Advice from a friend comes to mind, where he recommended 200 mg modafinil over 300 mg for exam preparation since the euphoric effect of the high at higher doses would distract from the task at hand. Similarly, I find Noopept a better mind enhancer since it lacks these euphoric properties that piracetam (or moreso Oxyracetam) posesses. Another user hit the nail on the head, IMHO, when he said that the overall effects compare to LSD without the hallucinations. I would add that it has a slight feeling of empathogenesis without the distinctive euphoria characteristic of MDMA.

I feel that LSD has the highest nootropic action, in that it not only accelerates certain cognitive functions, but allows (quoting DM Turner) "a mind to see itself from vast and novel perspectives". Consequently, it shouldn't surprise anyone that I remain partial to Noopept which feels similar to LSD. I suspect that ergot derivatives could provide many interesting and novel nootropics. Many use hydergine and consider it synergistic with the racetams. Albert Hoffman took it for many years, and now Alexander Shulgin also takes it (to remarkably successful effect I might add). Furthermore, ergot derivatives posess dopaminergic activity. While some such as bromocryptine have hepatotoxic properties, many other ergot derivatives could have a better safety profile. (e.g. Cabergoline)

Two other candidates come to my mind. First I consider modafinil, which has nootropic properties long after the initial stimulation has subsided, making it a likely candidate for a popular nootropic. Personally, I find the stimulation to interfere with the "calm but alert" mindset that characterizes the racetams. Perhaps other derivatives would posess a more desirable pharmacological profile. Secondly, I consider BTCP (Benocyclidine), a dopamine reuptake inhibitor despite belonging to the arylcyclohexylamine family, to have significant potential. I do not posess qualitative data on it, but it intrigues me. I remain curious about it and welcome comments form any bluelighters with knowledge of BTCP! The arylcyclohexylamines have a broad range of possible structures with a myriad of properties, it would not surprise me if a future nootropic came from this class of compounds.

Racetams partly work by upregulating BDNF and NGF in the hippocampus. cAMP, another important enzyme, also contributes to metabolism. Interestingly, stimulation of D1 receptors causes upregulation of cAMP, however stimulation of D2 receptors causes downregulation. The dissociatives PCP and Salvinorin A stimulate D2, however I can only think of one molecule of the top of my head that stimulates D1 receptors only: the endogeneous psychedelic DMT. Perhaps a pure D1 receptor agonist might function as an effective nootropic?

Haha, I finally ran out of stuff to say. Decided to make this a good first post. ;)
 
Great first post monad :)

I was searching the BL for info about Cerebrolysin. I found many non substance-users loving the hell out of it, and I was hoping that people who are more familiar with ingesting/injecting relatively unknown substances would be more excited about it.

To give some info, Cerebrolysin is made from the small peptides from pig brains. These peptides are shown to bind to endogenous receptors for NGF, BDNF, IGF etc. Also since the peptides are small enough, they can cross the blood brain barrier. This drug is indicated for dementia, stroke and other brain injuries. I stumbled upon papers, which tell how big doses of cerebrolysin almost reverses stroke, and other brain injuries. And for the dementia part, a cycle of 28 days results in statistically significant cognitive improvement, even AFTER 9 MONTHS. Well, that is something.

Google search can lead any interested folks to otherwise healthy people (with drug seeking behavior of course!) trying Cerebrolysin. They report very strong improvements (much stronger than subtle improvements our long tried AMPAkines) in mental clarity, energy and wakefulness, verbal fluency and so forth. Good portion reports anxiolytic effects, some say increased sex drive, and self confidence. As for side effects, what people only seem to be complaining is "burning sensation at the injection site."

To list some caveats, one is that you have to inject it either IM or very very slowly IV. Second is that it is a prescription medicine (though the web is full of stores selling it). Third is that it cost pretty pretty hefty, 300-400 USD for a 4 week cycle.

Go get em lads!
 
wormdevil said:
Great first post monad :)

I was searching the BL for info about Cerebrolysin. I found many non substance-users loving the hell out of it, and I was hoping that people who are more familiar with ingesting/injecting relatively unknown substances would be more excited about it.

To give some info, Cerebrolysin is made from the small peptides from pig brains. These peptides are shown to bind to endogenous receptors for NGF, BDNF, IGF etc. Also since the peptides are small enough, they can cross the blood brain barrier. This drug is indicated for dementia, stroke and other brain injuries. I stumbled upon papers, which tell how big doses of cerebrolysin almost reverses stroke, and other brain injuries. And for the dementia part, a cycle of 28 days results in statistically significant cognitive improvement, even AFTER 9 MONTHS. Well, that is something.

Google search can lead any interested folks to otherwise healthy people (with drug seeking behavior of course!) trying Cerebrolysin. They report very strong improvements (much stronger than subtle improvements our long tried AMPAkines) in mental clarity, energy and wakefulness, verbal fluency and so forth. Good portion reports anxiolytic effects, some say increased sex drive, and self confidence. As for side effects, what people only seem to be complaining is "burning sensation at the injection site."

To list some caveats, one is that you have to inject it either IM or very very slowly IV. Second is that it is a prescription medicine (though the web is full of stores selling it). Third is that it cost pretty pretty hefty, 300-400 USD for a 4 week cycle.

Go get em lads!
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You also can try "Semax" russian peptide nootropic, approved for uses in emergency situation and after strokes. Good thing that you can use it nasally.

About Metaprote - guys i can't find any researches about this substance on english, sorry.
May be later i will try to translate something. But as i understand it more "physically improving", you tend to resist cold, sleep less(and didn't get brain fog) and so on.
 
Not to rain on your parade, but in my experience Russian and Chinese research on "wonder drugs" tends to be fairly biased
 
Yeah, a peptide drug that has relatively unknown composition other than "derived from pig brain" doesn't give me a warm fuzzy feeling
 
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