1725 replies to this topic

[dreth7]

I second what Q Did It said. I've followed this thread from the beginning curiously awaiting information. We are an entire community here whether or not we are "all" involved in the initial purchase/ trial. Likewise, the majority of classmates I have in medical school are beyond skeptical of nootropics and the like. It is counterintuitive, but the vast majority follow the mantra that the mainstream is correct.

[Major Legend]

Just an update:

The orders have been placed and the PRL is in production . Its only a matter of time till we receive our samples of PRL-8-53. People that I am mailing samples to should receive theirs in 5-7 week and persons receiving their samples from science guy about 6-7 weeks.

If this goes well(the chemical works) we can submit a request to NovoChemy for a 200g or 1kg quantity at a reduced price. I have not sent the request yet but if all goes well we can probably get 1kg for about 3k to 5k. Or we could just see if we can get a lab (US and/or UK) say SunShineNootropics to stock it and recommend a few suppliers to them NovoChemy being one of them.

Also concerning future group buys we will have a much better system in place for the payment and mailing. T&W will actually mail out all the individual samples to participants if desired (shipping included in final quote). Though it will cost more initially but would work out to be about the same as shipping from receivers; which would mean that receivers would no longer be needed. Thusparticipants would receive samples sooner. So for future group buys when possible I say we go with T&W, even if the price may be a little higher than some labs.

yes, i told you about T&W, they are legit

And the good old simple, "Why not?", why do you want to be an elite and limit others from getting the (unfair?) boost you're getting?

The answer is pretty simple - because most people want to improve certain aspects to out perform others. Life is a competition, society is a competition, there is no way around it.

The higher you climb the more FREE and more OPTIONS open up to how you live your life, baring unavoidable misery events. If you have good parents, good genetics and make it into Stanford early on, THE WORLD OPENS UP TO YOU, but how many people get to go to Stanford? Do we want those privileges to light-leap even further away from the underachievers? Do you want them to rule your life more than they already do?

If everyone can improve the same manner, then the "elite" of the current world will keep being elite, and there will never be a chance for the underdog to move up. Exams and work will simply become harder and tougher, and so on - because everyone will become smarter, or we will lead to these substances being banned.

I would also add that the elite often have gotten to the elite by having UNFAIR ADVANTAGES in the first place, like genes, wealth, connections, sociability, bullying others.

The longer we dig into this discussion, the more we open the can of worms. I've simply stated my opinions, let's not derail this discussions into ethics - if people agree with me then they will try to keep information away from the mainstream whilst promoting an open forum as much as possible - including those who have actively participated and risked their lives in gaining this information (or any other more advanced methods they can think of) - for their own good.

If the endeaver is simply for the "betterment of mankind" than I can think of many more avenues that should have our undivided attention at the moment like sclerosis, cancer and dementia.

And finally like I say, we are only discussing the INEVITABLE - I just hope and wish deeply those of us invested and many of us who genuinely need this help can have small head start.

well spoken.

Agree in part. We will have a head start and we could start a new thread as planned but just make it private but is that really fair. Do we not at least owe it to the community to report back with what we have found (granted hopefully it’s something good)? We could make it open to members only. That would seem fair and I think (correct me if I am wrong) what a private thread does anyway.

So let’s say the chemical PRL is a great success and it gives us near perfect memories (at least long term). Hopefully it does not impair short term memory as the CILTEP stack does but Piracetam does seem to alleviate it well enough though. We make a private/closed thread for PRL what do we do after it’s a success (theoretically speaking)? We make a new bigger group buy order and try to get ahead (mentally advance) of everyone else (who is everyone else other than people already using nootropics) before they find out and try to do the same?
Most people I have talked to about nootropics are very skeptical and do not like the idea of putting chemicals in their bodies that have not been FDA approved (I for one do not like the FDA and Big Pharma).
I think we do not have have anything to fear from this getting spread and if what we are doing is a huge success don’t expect to hear about it in the Media or any popular channel. They are good at keeping things like this out; they don’t want it! Very rarely is anything of “Nootropic” value mentioned and if it is its one of those hair brain ideas that will never work. The governments don’t want their populations as a whole getting smarter and neither do the big business it would create mayhem and upset many systems (fore once people would see though the vile that is cast over their eyes). “Slow and steady” is their motto for human advancement. We are pioneers in human evolution! We seek to better ourselves though chemicals, mediation, tones and such. When we finally find something huge (and I think it will be soon) its then and only then that we need fear. There have been many advances in science and bio that would shock us but they are kept secret for obvious reasons. And PRL is not a secret we found out about it and it is available for purchase on web sites like Novo and ArkPharm(US based Company).

1 ) I do not think that these research chemicals in group buys will have be the game changers, the improvements upon current nootropics like caffeine are likely to be incremental if any, the state of past attempts have shown us that nootropics are have a small margin of effect on medically healthy individuals (even those with depression, anxiety, brain fog, autism.) I raised the issue, because as a community for reasons stated in my past 2 posts, WE ARE ALL INVESTED in this - and this media wildfire problem is looming on the horizons.

2) [removed due to irrelevancy]

3) I do not think that the government has any say in this matter, nor do I think they are out to make us dumber/more obedient citizens, if there are any such people it would be the super rich, certain corporations and the financial system, even then I don't think they are out to make us dumber, people act out in their own best interests, and via many complexity events affect other people in larger scale

4) The game changers will happen , and the media will DEFINITELY cover it, no doubt about it, there are so many platforms for information relay now, to name the few you verge, wire, fast company, monocle all these could do with an article like this, not to mention the numerous prominent blogs on the internet, once this becomes mainstream there would be literally millions and millions of people exposed to this new found information. Information that we have spent years messing with our bodies and experimental chemicals to obtain.

5) So the question is, how do we CONTROL the flow of information so the TIPPING POINT doesn't arise immediately when we figure out some amazing combination, that makes CILTEP look like childplay. For ages the approach in longecity has been an amazing one - an open forum where people post objective information and experiences, lots of people have benefitted simply by reading this forum - it would be a sin to not return information to the community, but if we are to control information we have to make it a private party one day, for every contributor there are probably thousands of docile viewers who hope to gain from us.

So this is what I propose:

a) Each group buy forms each own cluster, or say "research chemical group", so yes private threads are needed - i'm not sure how we achieve that?

b) Group buys have its own discussions/results, its own continuous purchases, its own rules, I would advocate a democratic system for this, the goal is to contribute to the longecity community eventually but to "keep the hype down". I also think its reasonable to let the receivers to get a token donation for all the work they put in to organizing this.

c) Group buys are free to add new members, but like mutual funds the capacity of the group buys can be limited i.e. closed to newer members

d) Group buys keep information to itself, and only through voting can the information be released to the community/public, the degree at which the information is released is decided by the group buy, though I would advocate useful information to be given out
for the community to identify further avenues of approach. WE MUST list the pros and CONS of the chemicals, HYPE is a dangerous thing, it's what will make this thing explode.

e) people are free to reveal information after the group buy has ceased activity after 6 months (maybe we should make this longer, not sure if we can enforce such a rule anyways, maybe we can make this a general goodwill agreement?)

f) group buys have both a public thread and a private thread available to only group buy members - this will keep freeflow of information on both ends.

^ So this keeps information flowing, but the information is controlled, people who want to experiment can keep forming new group buys, with the clusters releasing information less frequently than an otherwise all out open discussion, when the tipping point appears it will delay the traction of the chemical becoming mainstream.

REMEMBER we are not here to be against ourselves, but we want to protect ourselves and our bodily...investments from the much larger intranet and the mainstream which does consist of many scary people who we don't really want to get excited about this. Google "memory enhancer" or any cognitive term and you will arrive at longecity - everyone is literally a few keyboard presses away from here. Again I should emphasize most of us here have spent years on this. I thank those who have spent years contributing to my wellbeing too, I think this action is worth thinking about for the future benefit of those in need invested in the future as a whole.

What do you guys thinks?

I can just go on and on, I have reached the limits of my contribution in this matter, those interested in this discussion should read the last 2 pages.

[Q did it!]

Just an update:

The orders have been placed and the PRL is in production . Its only a matter of time till we receive our samples of PRL-8-53. People that I am mailing samples to should receive theirs in 5-7 week and persons receiving their samples from science guy about 6-7 weeks.

If this goes well(the chemical works) we can submit a request to NovoChemy for a 200g or 1kg quantity at a reduced price. I have not sent the request yet but if all goes well we can probably get 1kg for about 3k to 5k. Or we could just see if we can get a lab (US and/or UK) say SunShineNootropics to stock it and recommend a few suppliers to them NovoChemy being one of them.

Also concerning future group buys we will have a much better system in place for the payment and mailing. T&W will actually mail out all the individual samples to participants if desired (shipping included in final quote). Though it will cost more initially but would work out to be about the same as shipping from receivers; which would mean that receivers would no longer be needed. Thusparticipants would receive samples sooner. So for future group buys when possible I say we go with T&W, even if the price may be a little higher than some labs.

yes, i told you about T&W, they are legit

And the good old simple, "Why not?", why do you want to be an elite and limit others from getting the (unfair?) boost you're getting?

The answer is pretty simple - because most people want to improve certain aspects to out perform others. Life is a competition, society is a competition, there is no way around it.

The higher you climb the more FREE and more OPTIONS open up to how you live your life, baring unavoidable misery events. If you have good parents, good genetics and make it into Stanford early on, THE WORLD OPENS UP TO YOU, but how many people get to go to Stanford? Do we want those privileges to light-leap even further away from the underachievers? Do you want them to rule your life more than they already do?

If everyone can improve the same manner, then the "elite" of the current world will keep being elite, and there will never be a chance for the underdog to move up. Exams and work will simply become harder and tougher, and so on - because everyone will become smarter, or we will lead to these substances being banned.

I would also add that the elite often have gotten to the elite by having UNFAIR ADVANTAGES in the first place, like genes, wealth, connections, sociability, bullying others.

The longer we dig into this discussion, the more we open the can of worms. I've simply stated my opinions, let's not derail this discussions into ethics - if people agree with me then they will try to keep information away from the mainstream whilst promoting an open forum as much as possible - including those who have actively participated and risked their lives in gaining this information (or any other more advanced methods they can think of) - for their own good.

If the endeaver is simply for the "betterment of mankind" than I can think of many more avenues that should have our undivided attention at the moment like sclerosis, cancer and dementia.

And finally like I say, we are only discussing the INEVITABLE - I just hope and wish deeply those of us invested and many of us who genuinely need this help can have small head start.

well spoken.

Agree in part. We will have a head start and we could start a new thread as planned but just make it private but is that really fair. Do we not at least owe it to the community to report back with what we have found (granted hopefully it’s something good)? We could make it open to members only. That would seem fair and I think (correct me if I am wrong) what a private thread does anyway.

So let’s say the chemical PRL is a great success and it gives us near perfect memories (at least long term). Hopefully it does not impair short term memory as the CILTEP stack does but Piracetam does seem to alleviate it well enough though. We make a private/closed thread for PRL what do we do after it’s a success (theoretically speaking)? We make a new bigger group buy order and try to get ahead (mentally advance) of everyone else (who is everyone else other than people already using nootropics) before they find out and try to do the same?
Most people I have talked to about nootropics are very skeptical and do not like the idea of putting chemicals in their bodies that have not been FDA approved (I for one do not like the FDA and Big Pharma).
I think we do not have have anything to fear from this getting spread and if what we are doing is a huge success don’t expect to hear about it in the Media or any popular channel. They are good at keeping things like this out; they don’t want it! Very rarely is anything of “Nootropic” value mentioned and if it is its one of those hair brain ideas that will never work. The governments don’t want their populations as a whole getting smarter and neither do the big business it would create mayhem and upset many systems (fore once people would see though the vile that is cast over their eyes). “Slow and steady” is their motto for human advancement. We are pioneers in human evolution! We seek to better ourselves though chemicals, mediation, tones and such. When we finally find something huge (and I think it will be soon) its then and only then that we need fear. There have been many advances in science and bio that would shock us but they are kept secret for obvious reasons. And PRL is not a secret we found out about it and it is available for purchase on web sites like Novo and ArkPharm(US based Company).

1 ) I do not think that these research chemicals in group buys will have be the game changers, the improvements upon current nootropics like caffeine are likely to be incremental if any, the state of past attempts have shown us that nootropics are have a small margin of effect on medically healthy individuals (even those with depression, anxiety, brain fog, autism.) I raised the issue, because as a community for reasons stated in my past 2 posts, WE ARE ALL INVESTED in this - and this media wildfire problem is looming on the horizons.

2) [removed due to irrelevancy]

3) I do not think that the government has any say in this matter, nor do I think they are out to make us dumber/more obedient citizens, if there are any such people it would be the super rich, certain corporations and the financial system, even then I don't think they are out to make us dumber, people act out in their own best interests, and via many complexity events affect other people in larger scale

4) The game changers will happen , and the media will DEFINITELY cover it, no doubt about it, there are so many platforms for information relay now, to name the few you verge, wire, fast company, monocle all these could do with an article like this, not to mention the numerous prominent blogs on the internet, once this becomes mainstream there would be literally millions and millions of people exposed to this new found information. Information that we have spent years messing with our bodies and experimental chemicals to obtain.

5) So the question is, how do we CONTROL the flow of information so the TIPPING POINT doesn't arise immediately when we figure out some amazing combination, that makes CILTEP look like childplay. For ages the approach in longecity has been an amazing one - an open forum where people post objective information and experiences, lots of people have benefitted simply by reading this forum - it would be a sin to not return information to the community, but if we are to control information we have to make it a private party one day, for every contributor there are probably thousands of docile viewers who hope to gain from us.

So this is what I propose:

a) Each group buy forms each own cluster, or say "research chemical group", so yes private threads are needed - i'm not sure how we achieve that?

b) Group buys have its own discussions/results, its own continuous purchases, its own rules, I would advocate a democratic system for this, the goal is to contribute to the longecity community eventually but to "keep the hype down". I also think its reasonable to let the receivers to get a token donation for all the work they put in to organizing this.

c) Group buys are free to add new members, but like mutual funds the capacity of the group buys can be limited i.e. closed to newer members

d) Group buys keep information to itself, and only through voting can the information be released to the community/public, the degree at which the information is released is decided by the group buy, though I would advocate useful information to be given out
for the community to identify further avenues of approach. WE MUST list the pros and CONS of the chemicals, HYPE is a dangerous thing, it's what will make this thing explode.

e) people are free to reveal information after the group buy has ceased activity after 6 months (maybe we should make this longer, not sure if we can enforce such a rule anyways, maybe we can make this a general goodwill agreement?)

f) group buys have both a public thread and a private thread available to only group buy members - this will keep freeflow of information on both ends.

^ So this keeps information flowing, but the information is controlled, people who want to experiment can keep forming new group buys, with the clusters releasing information less frequently than an otherwise all out open discussion, when the tipping point appears it will delay the traction of the chemical becoming mainstream.

REMEMBER we are not here to be against ourselves, but we want to protect ourselves and our bodily...investments from the much larger intranet and the mainstream which does consist of many scary people who we don't really want to get excited about this. Google "memory enhancer" or any cognitive term and you will arrive at longecity - everyone is literally a few keyboard presses away from here. Again I should emphasize most of us here have spent years on this. I thank those who have spent years contributing to my wellbeing too, I think this action is worth thinking about for the future benefit of those in need invested in the future as a whole.

What do you guys thinks?

I can just go on and on, I have reached the limits of my contribution in this matter, those interested in this discussion should read the last 2 pages.

Its a good idea but I am not sure if longecity can do private threads. If not we could start a public thread here than have a private froum or site where we could go to once the group buys are initiated or a group email of some sort.

[Major Legend]

I for one am interested in the artistic possibilities. I cannot imagine how good a musician I would be with a near-perfect memory. My creativity is through the roof but I've got as poor a memory as anyone I know (elderly excluded). I also fantasize about reading novels and philosophical works and being able to recall every detail. Maybe I'm in the minority, but having a "competitive advantage" over the next guy is the furthest thing from my mind. That isn't to say I support spreading this to everyone, which does seem unfair to the pioneers. I'm just focused on how it will improve my own mind in pursuit of my own enlightenment and expression.

I also agree with this, I too enjoy the beauty of limitless (relatively more limitless anyways) of intelligence and creativity - it has been something that has to an extent been taken away from me due to an accident, I seek to regain that feeling of being immersed in a world of beauty - however the competitive uses of enhancers is the darker side of the discussion - how does society define good? good is also because you can do enjoy something others can't, good makes you the better one out of all the lesser ones.

I fear the idiots (not low intelligence, but of heartless intentions) - the general public unfortunately. Your heart is in the right place.

[Q did it!]

I for one am interested in the artistic possibilities. I cannot imagine how good a musician I would be with a near-perfect memory. My creativity is through the roof but I've got as poor a memory as anyone I know (elderly excluded). I also fantasize about reading novels and philosophical works and being able to recall every detail. Maybe I'm in the minority, but having a "competitive advantage" over the next guy is the furthest thing from my mind. That isn't to say I support spreading this to everyone, which does seem unfair to the pioneers. I'm just focused on how it will improve my own mind in pursuit of my own enlightenment and expression.

I also agree with this, I too enjoy the beauty of limitless (relatively more limitless anyways) of intelligence and creativity - it has been something that has to an extent been taken away from me due to an accident, I seek to regain that feeling of being immersed in a world of beauty - however the competitive uses of enhancers is the darker side of the discussion - how does society define good? good is also because you can do enjoy something others can't, good makes you the better one out of all the lesser ones.

I fear the idiots (not low intelligence, but of heartless intentions) - the general public unfortunately. Your heart is in the right place.

Ok you made me laugh a bit with the "I fear idiots" line. But seriously I get what you mean just made my day a little brighter, thanks.

What accident if you don't mind me asking took something from you?

[Major Legend]

Answered you with a PM.

mhmh thinking about it, the research cluster idea could bring order to the current chaos, which could make it easier for the mainstream to understand the information too. I don't know if this method of control will actually make it the"media wildfire" scenario more likely...thoughts?

to counter that we should avoid posting "magazine like ":" "or very statistical relevant" summarized information for entire groups.

An example of how to avoid too magazine useful would be:

[Group buy blah blah blah] has now decided to release results for their group buy.

Participants : 40
Overall Feedback: Group buy was a success, members generally satisfied with the result. 14 out of 40 did not feel any effects.
Duration of testing: 7 months.
Overall Pros: Long term memory improvement, visual clarity
Overall Cons: Fatigue, Working memory problems, does not seem to work for people with good memory.

Further research avenues suggest: research chemical xyz, combinations with xyz
People who may benefit from this: depression, long term recall problems.

This group will not be answering any questions regarding the details of this group buy, if you would like to discuss starting another group buy please start another thread.

Edited by Major Legend, 29 April 2013 - 05:16 AM.

[DamnedOwl]

I'm not actually part of this group buy myself (unfortunately missed the boat on that), but I am part of the NSI-189 group buy, so I suppose since this discussion is currently about how we proceed with the next stage of actually trialling these compounds as a group in general, then I guess my two cents might be worth my adding.

Anyway, I have to say, I was somewhat repelled by the idea to make these groups private when I first saw it mooted a couple of days ago.

And still, the 'elitist' overtones resonate to a degree with me.

However, I can't deny that I have found some of the arguments above fairly persuasive.

At least, anyway, those arguments with regards to trying to prevent hype. And in this respect the prevention of hype is as much about controlling its ill-effects both within and outside these suggested closed-groups.

Minimizing the hype outside the closed-group has already been covered, but within the group itself, hype can also perhaps be minimized (by closing off the group) by eliminating the risk of proselytizers, which I'm sure we've all seen happen in so, so, many threads down the years. The "OMG, you must try this stuff!!!" type of post (I exaggerate here for effect, but you get the idea). But since those within the group will all be taking 'this stuff' already, there'll be no 'audience' to try to persuade, and so hopefully the group members would find it much easier to give an honest account (of at least the subjective experience, if not any objective measures (like test scores) we may attempt to gather).

[megatron]

I agree with Major Legend of all my heart. The public exposure has to be controlled. Group buy participants should get a big head start.

Also, I want Dihexa to be the next group buy. To me it seems that a drug promoting synaptogenesis has a greater potential of improving ones cognition than an ampakine drug.

[Reformed-Redan]

Also, I want Dihexa to be the next group buy. To me it seems that a drug promoting synaptogenesis has a greater potential of improving ones cognition than an ampakine drug.

Can you qualify that statement?

[megatron]

Also, I want Dihexa to be the next group buy. To me it seems that a drug promoting synaptogenesis has a greater potential of improving ones cognition than an ampakine drug.

Can you qualify that statement?

From what I've read to now it seems like more intelligent persons have a higher density of synapses. Personally, the only effect I got from Aniracetam was tiredness, and I haven't noticed effects from Sunifiram yet.

[Q did it!]

Also, I want Dihexa to be the next group buy. To me it seems that a drug promoting synaptogenesis has a greater potential of improving ones cognition than an ampakine drug.

Can you qualify that statement?

I am not really on the whole Dihexa boat. The chem just does not have enough studies on it for me and are there not a few guys in another thread who are testing it or are going to be soon. I say we wait to see what they find before we go to the trouble of organizing a group buy for it. The return just does not seem all that good, at least to me. IDRA-21 or BPAP seem like much more likely candidates for the next group buy (which should really be no soon than 4 weeks time). BPAP sounds cool but it seems to be a jazzed up version of selegiline though it does stand to be many times better. IDRA-21 seems like it could be a very nice nootropic. But also its important to realize that New Star Nootropics will have Coluracetam and Unifiam soon for testing. So we as a community will have: NSI-89, PRL-8-53, Sunifiam, Zimbin, Coluracetam and Unifiam to test. So with all the stuff going on in this forum I thing we can slow down a bit, if only to allow our wallets a chance to recuperate

Edited by Q did it!, 29 April 2013 - 05:13 PM.

[megatron]

Also, I want Dihexa to be the next group buy. To me it seems that a drug promoting synaptogenesis has a greater potential of improving ones cognition than an ampakine drug.

Can you qualify that statement?

I am not really on the whole Dihexa boat. The chem just does not have enough studies on it for me and are there not a few guys in another thread who are testing it or are going to be soon. I say we wait to see what they find before we go to the trouble of organizing a group buy for it. The return just does not seem all that good, at least to me. IDRA-21 or BPAP seem like much more likely candidates for the next group buy (which should really be no soon than 4 weeks time). BPAP sounds cool but it seems to be a jazzed up version of selegiline though it does stand to be many times better. IDRA-21 seems like it could be a very nice nootropic. But also its important to realize that New Star Nootropics will have Coluracetam and Unifiam soon for testing. So we as a community will have: NSI-89, PRL-8-53, Sunifiam, Zimbin, Coluracetam and Unifiam to test. So with all the stuff going on in this forum I thing we can slow down a bit, if only to allow our wallets a chance to recuperate

Absolutely. Also, NSI-189 probably needs several months of usage to be tested properly, as we are in fact (hopefully) growing new neurons. So for the participants (myself included) taking part in both group buys probably don't need to test any other drugs till fall or even winter, assuming growing new neurons is a time consuming process. And of course we want to test these experimental drugs separately and not at the same time. I don't see any reason to join more group buys other than possibly more PRL 8-53 and NSI-189 before Christmas.

However, it depends on the price of other drugs. If group buys are initiated for other drugs as well, I may join anyway. The threads for those substances (as for NSI-189 and PRL 8-53) are probably going private, and I can't take the risk of those drugs being successful and not getting the info, lol! I really, really hope we make the results threads private.

Edited by Megatrone, 29 April 2013 - 05:36 PM.

[sunshinefrost]

Absolutely. Also, NSI-189 probably needs several months of usage to be tested properly, as we are in fact (hopefully) growing new neurons.

Did the research show that NSI-189 needed to be taken several months ? i though it was a 28 days period... can't remember, ironically.

[dare2winit]

I was discussing PRL-8-53 with a PA friend of mine and she asked me if I had done the research into what PRL-8-53 metabolizes as. Does anyone have some input on this?

[Nattzor]

I was discussing PRL-8-53 with a PA friend of mine and she asked me if I had done the research into what PRL-8-53 metabolizes as. Does anyone have some input on this?

Going to bed now, but if you look at the original study, last footnote you'll see what it metabolites to, the metabolite is also active.

[EngineeringGenius]

I'd like to state my intention to participate in the next group buy. I do hope someone is keeping a list of willing future participants since not everyone is able to monitor the forums consistently, and I would hate to know I got left out because of that.

[Q did it!]

Ok this is cool. Someone added PRL-8-53 to Wikipedia http://en.wikipedia.org/wiki/PRL-8-53. Hopefully after our testing we can contribute a little bit more data

[Reformed-Redan]

Don't know about you guys; but, I'm saving what I can for IDRA-21.

[Q did it!]

Don't know about you guys; but, I'm saving what I can for IDRA-21.

Same here but what about a group buy (but not for some time) for PRL-8-147?

[Reformed-Redan]

Don't know about you guys; but, I'm saving what I can for IDRA-21.

Same here but what about a group buy (but not for some time) for PRL-8-147?

Well if this compound is true to its description, maybe. Problem is with toxicology and the such. :?

[sunshinefrost]

Don't know about you guys; but, I'm saving what I can for IDRA-21.

Same here but what about a group buy (but not for some time) for PRL-8-147?

I just opened a payitsquare page to collect funds for prl-8-147.... Just kidding, i'll wait after i'm done with 853 and 189.

[Reformed-Redan]

Don't know about you guys; but, I'm saving what I can for IDRA-21.

Same here but what about a group buy (but not for some time) for PRL-8-147?

We can also check out maybe, Pitolisant or Ciproxifan. They are related to the nootropic and wakefulness producing effects of Provigil/Modafinil, Armodafinil, and Adrafinil. They also don't look like a hell hard to synthesize, especially Pitolisant. They have nootropic effects and counteract ADD, like Modafinil and other disorders that induce cognitive decline. What seems really appealing to me about Pitolisant or Ciproxifan is that when I was asking for quotes earlier for quantities from CH, the prices were reasonable, no negative isomers or anything like that. I also love the idea of just being fully aware and awake of my surroundings.

Histamine-3 autoreceptor antagonists like Ciproxifan have been shown to increase the amount of histamine that is released into the synaptic cleft that latter enchances glutamergic transmission in the hippocampus and dopamine and norepinephrinein the PFC. Good stuff and clinical results see very positive,

Edited by yadayada, 30 April 2013 - 05:30 AM.

[Reformed-Redan]

BF2.649 [1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride], a nonimidazole inverse agonist/antagonist at the human histamine H3 receptor: Preclinical pharmacology.

Ligneau X, Perrin D, Landais L, Camelin JC, Calmels TP, Berrebi-Bertrand I, Lecomte JM, Parmentier R, Anaclet C, Lin JS, Bertaina-Anglade V, la Rochelle CD, d'Aniello F, Rouleau A, Gbahou F, Arrang JM, Ganellin CR, Stark H, Schunack W, Schwartz JC.

Source

Bioprojet-Biotech, Saint Grégoire, France.

Abstract


Histamine H3 receptor inverse agonists are known to enhance the activity of histaminergic neurons in brain and thereby promote vigilance and cognition. 1-{3-[3-(4-Chlorophenyl)propoxy]propyl}piperidine, hydrochloride (BF2.649) is a novel, potent, and selective nonimidazole inverse agonist at the recombinant human H3 receptor. On the stimulation of guanosine 5'-O-(3-[35S]thio)triphosphate binding to this receptor, BF2.649 behaved as a competitive antagonist with a Ki value of 0.16 nM and as an inverse agonist with an EC50 value of 1.5 nM and an intrinsic activity approximately 50% higher than that of ciproxifan. Its in vitro potency was approximately 6 times lower at the rodent receptor. In mice, the oral bioavailability coefficient, i.e., the ratio of plasma areas under the curve after oral and i.v. administrations, respectively, was 84%. BF2.649 dose dependently enhanced tele-methylhistamine levels in mouse brain, an index of histaminergic neuron activity, with an ED50 value of 1.6 mg/kg p.o., a response that persisted after repeated administrations for 17 days. In rats, the drug enhanced dopamine and acetylcholine levels in microdialysates of the prefrontal cortex. In cats, it markedly enhanced wakefulness at the expense of sleep states and also enhanced fast cortical rhythms of the electroencephalogram, known to be associated with improved vigilance. On the two-trial object recognition test in mice, a promnesiant effect was shown regarding either scopolamine-induced or natural forgetting. These preclinical data suggest that BF2.649 is a valuable drug candidate to be developed in wakefulness or memory deficits and other cognitive disorders.

The brain H₃-receptor as a novel therapeutic target for vigilance and sleep–wake disorders

• R. Parmentier^{a, b, c},
• C. Anaclet^{a, b},
• C. Guhennec^c,
• E. Brousseau^c,
• D. Bricout^c,
• T. Giboulot^c,
• D. Bozyczko-Coyne^d,
• K. Spiegel^a,
• H. Ohtsu^e,
• M. Williams^d,
• J.S. Lin^{a, b, ,}

• ^a INSERM-U628, Integrated Physiology of Brain Arousal Systems, 69373 Lyon, France
• ^b Department of Experimental Medicine, Faculty of Medicine, Claude Bernard University, 69373 Lyon, France
• ^c Worldwide Discovery Research, Cephalon, Inc., 94700 Maisons-Alfort, France
• ^d Worldwide Discovery Research, Cephalon, Inc., West Chester, PA 19380-4245, USA
• ^e Department of Cellular Pharmacology, Tohoku University, School of Medicine, Sendai 980-8575, Japan

• http://dx.doi.org/10...bcp.2007.01.002, How to Cite or Link Using DOI

• 
  Permissions & Reprints

Abstract

Brain histaminergic neurons play a prominent role in arousal and maintenance of wakefulness (W). H₃-receptors control the activity of histaminergic neurons through presynaptic autoinhibition. The role of H₃-receptor antagonists/inverse agonists (H₃R-antagonists) in the potential therapy of vigilance deficiency and sleep–wake disorders were studied by assessing their effects on the mouse cortical EEG and sleep–wake cycle in comparison to modafinil and classical psychostimulants. The H₃R-antagonists, thioperamide and ciproxifan increased W and cortical EEG fast rhythms and, like modafinil, but unlike amphetamine and caffeine, their waking effects were not accompanied by sleep rebound. Conversely, imetit (H₃R-agonist) enhanced slow wave sleep and dose-dependently attenuated ciproxifan-induced W, indicating that the effects of both ligands involve H₃-receptor mechanisms. Additional studies using knockout (KO) mice confirmed the essential role of H₃-receptors and histamine-mediated transmission in the wake properties of H₃R-antagonists. Thus ciproxifan produced no increase in W in either histidine-decarboxylase (HDC, histamine-synthesizing enzyme) or H₁- or H₃-receptor KO-mice whereas its waking effects persisted in H₂-receptor KO-mice. These data validate the hypothesis that H₃R-antagonists, through disinhibition of H₃-autoreceptors, enhancing synaptic histamine that in turn activates postsynaptic H₁-receptors promoting W. Interestingly amphetamine and modafinil, despite their potent arousal effects, appear unlikely to depend on histaminergic mechanism as their effects still occurred in HDC KO-mice. The present study thus distinguishes two classes of wake-improving agents: the first acting through non-histaminergic mechanisms and the second acting via histamine and supports brain H₃-receptors as potentially novel therapeutic targets for vigilance and sleep–wake disorders.

Correlation between ex vivo receptor occupancy and wake-promoting activity of selective H3 receptor antagonists.

Le S, Gruner JA, Mathiasen JR, Marino MJ, Schaffhauser H.

Source

World Wide Discovery Research, CNS Biology, Cephalon, Inc., 145 Brandywine Parkway, West Chester, PA 19380, USA. sle@cephalon.com

Abstract


The histamine H3 receptor (H3R) modulates the release of neurotransmitters that are involved in vigilance, cognition, and sleep-wake regulation. H3R antagonism has been proposed as a novel approach to the treatment of cognitive and attention deficit as well as sleep disorders. It is apparent that H3R antagonists produce pharmacological effects in preclinical animal models across a wide dose range. Several H3R antagonists were reported to be effective at producing cognitive enhancing effects at low doses, while producing robust wake enhancement at higher doses. To better understand the effect of H3R antagonists across a broad dose range, an ex vivo receptor binding assay has been used to estimate the degree of H3R occupancy in vivo. The H3R antagonists ciproxifan, thioperamide, GSK189254 (6-[(3-cyclobutyl-2,3,4,5-tetrahydro-1H-3-benzazepin-7-yl)oxy]-N-methyl-3-pyridinecarboxamide hydrochloride), and ABT-239 ([4-(2-{2-[(2R)-2-methylpyrrolidinyl]ethyl}-benzofuran-5-yl)benzonitrile) produced wake-promoting activity in vivo and a dose-dependent inhibition of H3R binding ex vivo. For ciproxifan, thioperamide, and GSK189254, a relatively low level of cumulative wake activity was linearly correlated with up to 80% of the receptor occupancy. In contrast, an abrupt break from linearity and a robust increase of waking activity was observed at doses that produce greater than 80% occupancy. Our results suggest a relatively small increase of waking activity at low levels of receptor occupancy that may be consistent with reported enhancement of attention and cognitive function. Robust waking activity at higher levels of H3R occupancy may be mechanistically different from activities at low levels of H3R occupancy.

[Psionic]

Don't know about you guys; but, I'm saving what I can for IDRA-21.

Same here but what about a group buy (but not for some time) for PRL-8-147?

We can also check out maybe, Pitolisant or Ciproxifan. They are related to the nootropic and wakefulness producing effects of Provigil/Modafinil, Armodafinil, and Adrafinil. They also don't look like a hell hard to synthesize, especially Pitolisant. They have nootropic effects and counteract ADD, like Modafinil and other disorders that induce cognitive decline. What seems really appealing to me about Pitolisant or Ciproxifan is that when I was asking for quotes earlier for quantities from CH, the prices were reasonable, no negative isomers or anything like that. I also love the idea of just being fully aware and awake of my surroundings.

Histamine-3 autoreceptor antagonists like Ciproxifan have been shown to increase the amount of histamine that is released into the synaptic cleft that latter enchances glutamergic transmission in the hippocampus and dopamine and norepinephrinein the PFC. Good stuff and clinical results see very positive,

Do you remember what was the quote for Ciproxifan?

[Web]

I for one am interested in the artistic possibilities. I cannot imagine how good a musician I would be with a near-perfect memory. My creativity is through the roof but I've got as poor a memory as anyone I know (elderly excluded). I also fantasize about reading novels and philosophical works and being able to recall every detail. Maybe I'm in the minority, but having a "competitive advantage" over the next guy is the furthest thing from my mind. That isn't to say I support spreading this to everyone, which does seem unfair to the pioneers. I'm just focused on how it will improve my own mind in pursuit of my own enlightenment and exp<b></b>ression.

I also agree with this, I too enjoy the beauty of limitless (relatively more limitless anyways) of intelligence and creativity - it has been something that has to an extent been taken away from me due to an accident, I seek to regain that feeling of being immersed in a world of beauty - however the competitive uses of enhancers is the darker side of the discussion - how does society define good? good is also because you can do enjoy something others can't, good makes you the better one out of all the lesser ones.

I fear the idiots (not low intelligence, but of heartless intentions) - the general public unfortunately. Your heart is in the right place.

Interesting, I'm in the same position my friend. Bad 'accident' in 2008 and have not been the same since. Memory was absolutely destroyed. Can't even remember what this nootropic is called without reading it first. Pathetic. Hopefully this will help people like us in a major way.

[megatron]

Absolutely. Also, NSI-189 probably needs several months of usage to be tested properly, as we are in fact (hopefully) growing new neurons.

Did the research show that NSI-189 needed to be taken several months ? i though it was a 28 days period... can't remember, ironically.

Yea, after updating myself (again) on the testing regimen and results; the hippocampus grew substantially after only 28 days. However, I really hope that 20% growth I read somewhere was not after 28 days only. That can't possibly be healthy?!

[warmin]

what is the daily dose (prl 8-53) by weight 82 kg?

[Nattzor]

I was discussing PRL-8-53 with a PA friend of mine and she asked me if I had done the research into what PRL-8-53 metabolizes as. Does anyone have some input on this?

"Note added in proof:

Following completion of this study it was found that the particular lot of PRL-8-53 that had been used contained a small amount of the desmethyl compound as admixture, which may also have contributed to the observed effects. However, since the compound is considered a metabolite of the parent compount (8-53), its presence should not detract from the findings"

So we know atleast 1 metabolite.

Don't know about you guys; but, I'm saving what I can for IDRA-21.

Same here but what about a group buy (but not for some time) for PRL-8-147?

Do you know any study on 8-147? I'd be more cautious with that.

what is the daily dose (prl 8-53) by weight 82 kg?

The study was done with 5 mg for everyone, but the patent says "0.01-4mg/kg (most preferable 0.05-1.2mg/kg)".

[Reformed-Redan]

Don't know about you guys; but, I'm saving what I can for IDRA-21.

Same here but what about a group buy (but not for some time) for PRL-8-147?

We can also check out maybe, Pitolisant or Ciproxifan. They are related to the nootropic and wakefulness producing effects of Provigil/Modafinil, Armodafinil, and Adrafinil. They also don't look like a hell hard to synthesize, especially Pitolisant. They have nootropic effects and counteract ADD, like Modafinil and other disorders that induce cognitive decline. What seems really appealing to me about Pitolisant or Ciproxifan is that when I was asking for quotes earlier for quantities from CH, the prices were reasonable, no negative isomers or anything like that. I also love the idea of just being fully aware and awake of my surroundings.

Histamine-3 autoreceptor antagonists like Ciproxifan have been shown to increase the amount of histamine that is released into the synaptic cleft that latter enchances glutamergic transmission in the hippocampus and dopamine and norepinephrinein the PFC. Good stuff and clinical results see very positive,

Here are two suppliers for Ciproxifan.
http://www.alibaba.c...ext=184025-19-2
Trust&We, a well known supplier of nootropics and another potentially cheaper supplier.
Worth inquiring as the price won't be astronomical. I haven't seen any tolerance issues with H3 antagonists.

Neurochemical and behavioral effects of ciproxifan, a potent histamine H3-receptor antagonist.

Ligneau X, Lin J, Vanni-Mercier G, Jouvet M, Muir JL, Ganellin CR, Stark H, Elz S, Schunack W, Schwartz J.

Source

Unité de Neurobiologie et Pharmacologie Moléculaire (U. 109) de I'INSERM, Centre Paul Broca, 2ter rue d'Alésia, 75014 Paris, France.

Abstract


Ciproxifan, i.e., cyclopropyl-(4-(3-1H-imidazol-4-yl)propyloxy) phenyl) ketone, belongs to a novel chemical series of histamine H3-receptor antagonists. In vitro, it behaved as a competitive antagonist at the H3 autoreceptor controlling [3H]histamine release from synaptosomes and displayed similar Ki values (0.5-1.9 nM) at the H3 receptor controlling the electrically-induced contraction of guinea pig ileum or at the brain H3 receptor labeled with [125I]iodoproxyfan. Ciproxifan displayed at least 3-orders of magnitude lower potency at various aminergic receptors studied in functional or binding tests. In vivo, measurement of drug plasma levels, using a novel radioreceptor assay in mice receiving ciproxifan p.o. or i.v., led to an oral bioavailability ratio of 62%. Oral administration of ciproxifan to mice enhanced by approximately 100% histamine turnover rate and steady state level of tele-methylhistamine with an ED50 of 0.14 mg/kg. Ciproxifan reversed the H3-receptor agonist induced enhancement of water consumption in rats with and ID50 of 0.09 +/- 0.04 mg/kg, i.p. In cats, ciproxifan (0.15-2 mg/kg, p.o.) induced marked signs of neocortical electroencephalogram activation manifested by enhanced fast-rhythms density and an almost total waking state. In rats, ciproxifan enhanced attention as evaluated in the five-choice task performed using a short stimulus duration. Ciproxifan appears to be an orally bioavailable, extremely potent and selective H3-receptor antagonist whose vigilance- and attention-promoting effects are promising for therapeutic applications in aging disorders.

[Reformed-Redan]

Cyclopropyl 4-(3-(1H-imidazol-4-yl)propyloxy)phenyl methanone (ciproxifan) is a novel reference antagonist for the histamine H₃ receptor. Despite the former Mitsunobu reaction the actual key reaction for preparation based on S_NAr for acylated fluoroaromatics with an additional cyclization in a one-pot procedure needs no chromatographic purification steps and results in good yields.