1725 replies to this topic

[Gerhard van Dieren]

Heyhey!

I recently stumbled across this article: http://www.whatareno...r/#!prettyPhoto.
And this even though it doesn't have any sources and the title might be very bold. It did tickle my curiosity.

I tried googling it too, but no results aside of the actual article I'm discussing now.

PLR 8-147: The Most Powerful Memory Enhancer?

Even in the late 70′s before nootropics started to gain popularity research uncovered some potent smart drugs. Some of these have been largely forgotten, despite the powerful benefits they may provide. One exceptional example is PLR 8-147. There has been little research performed on this compound for over 20 years. This is unfortunate because the research that has been done suggests it may be one of the most potent nootropic drugs ever developed.

PLR 8-147 and Memory

In High Frontiers, Durk Pearson describes the powerful mental benefits of PLR 8-147. An average person can memorize about 7 or 8 digits after looking at them for a second or two. With PLR, it is reported that this number jumps to an astounding 21 to 22 digits. This is an astounding 275% increase in memory. (For this specific test at least) He also states that a person suffering from amnesia was cured by a single dose.

The clinical studies I’ve been able to find aren’t quite as optimistic, but still suggest that PLR 8-147 could have potential as a powerful nootropic. In a clinical study by Nikolaus Hansl, volunteers who used PLR 8-147 displayed an improvement in verbal memory of 80%. This backs up earlier studies which have found similar boosts to memory from the drug. These benefits aren’t just limited to verbal memory either. One study exposed subjects to various geometric patterns, which they were later asked to draw from memory. As in previous studies, PLR 8-147 had a significant impact on the ability of the subjects to complete the task. Further studies using PLR 8-147 showed it to also improve the ability to perform mental math.

Other Benefits and Mechanism of Action

While human studies on PLR 8-147 have been limited to humans, tests to determine whether it may improve higher cognitive functions such as correlation and problem solving have only been performed on animals. Subjects in these studies also showed extremely significant improvements.

We still know very little about how PLR 8-147 works, besides that one of it’s main mechanisms of action is to enhance the brain’s response to the neurotransmitter acetylcholine. (Acetylcholine plays a vital role in learning and memory). We can only hope that as nootropics become more and more popular that there will be renewed interest in PLR 8-147; if it proves as effective as current research suggests the first company to bring it to market could stand to make a fortune.

So I was wondering, is anyone actually familiar with this substance? Or is it just a load bullcrap?

Edited by Gerhard van Dieren, 06 August 2012 - 06:22 PM.

[middpanther88]

Sounds fishy.

[Turnbuckle]

Perhaps they got the numbers wrong.

Here's another one, PRL-8-53, as in PRL-8-53: enhanced learning and subsequent retention in humans as a result of low oral doses of new psychotropic agent.

The effect of 3-(2-benzylmethylaminoethyl) benzoic acid methyl ester hydrochloride (PRL-8-53) on learning and on retention of verbal information in human subjects was investigated. Using the serial anticipation method under double-blind conditions it was found that PRL-8-53 causes slight improvement of acquisition. Retinetion of verbal information was found improved to a statistically significant degree (most P values better than 0.01, some better than 0.001). No significant changes were found for either visual reaction time or motor control after drug when compared with placebo values.

This same drug was described in far more glowing terms in a news story quoted in a forum--A team of Creighton University health science researchers is working with an experimental drug that could be just what the `absent-minded professor' has been needing for years.

Having established the spectrum of effectiveness in students, or at least a part of it, we wanted to learn how an older population subgroup would respond. A number of colleagues volunteered and took the verbal learning and retention test. This group as age 30 or older. As might be expected, rote memory did not come as easily to this group as it did to the younger students. The average retention after 24 hours when on placebo was just under three words out of a possible 12. The average retention after one week was two words. However, the same subjects, when learning subsequent to drug administration, retained an average of 5.85 words after 24 hours and 5.25 words after one week. Again the increases were statistically significant. The improvement expressed in percent of placebo performance was 108% for the 24 hour test and 152% for the one-week recall.

And the last post on that forum is refers to the drug you mentioned--

You're right that research on this particular compound is about 20 years old or longer...PRL 8-53, was listed and discussed in the journal of "Drugs of the Future." It's chemical structure was given in that publication. This publication is hard to find....you'll need to go to a medical interlibrary loan provider to locate this specific article. Also you might find it interesting that PRL-8-53, demonstrated enhanced performance in visual processing. Incidentally, PRL 8-53 was replaced by a more potent compound known as PRL 8-147, it's likely that you will not find any research on this preparation either...Dr. Hansl, at the time was also developing a similar type of compound which was discribed in the journal called the "Pharmacologist," A brief description of this compound was mentioned in a public press magazine known as "Longevity"....this magazine, as far as I know, is not in publication any longer. If you want to look into Dr. Hansl's earlier work, check out the Nebraska Academy of Sciences for further citations. I hope you find this information useful.

The inventor is Nikolaus Hansl. A patent from 1976--

http://patft.uspto.g...AND IN/Nikolaus

Edited by Turnbuckle, 06 August 2012 - 07:43 PM.

[Gerhard van Dieren]

Woah, thanks! That looks terribly interesting. I've done a bit of reading through the second source you provided, I don't see how this drug hasn't been developed any further.

[manic_racetam]

Looks like searching by the CAS# returns quite a few possible suppliers for the PRL-8-53 at least. Sent an inquiry off for a 10g sample. Very interesting stuff. Can't find much of anything on the PRL-8-147 though.

Anyone have any idea what human dosage was used in any of the studies on PRL-8-53?

[Turnbuckle]

Anyone have any idea what human dosage was used in any of the studies on PRL-8-53?

From the patent--

When utilized to enhance mental performance in higher mammals, the compounds of formula I, may be administered in oral dosages in the same range of from about 0.01 to about 4 mg/kg, preferably in the range of from about 0.01 to about 2 mg/kg, most preferably from about 0.05 to about 1.2 mg/kg. Parenteral dosages of about 10 to 100 times these levels are preferred in laboratory test animals.

http://patft.uspto.g...AND IN/Nikolaus

[manic_racetam]

Anyone have any idea what human dosage was used in any of the studies on PRL-8-53?

From the patent--

When utilized to enhance mental performance in higher mammals, the compounds of formula I, may be administered in oral dosages in the same range of from about 0.01 to about 4 mg/kg, preferably in the range of from about 0.01 to about 2 mg/kg, most preferably from about 0.05 to about 1.2 mg/kg. Parenteral dosages of about 10 to 100 times these levels are preferred in laboratory test animals.

http://patft.uspto.g...AND IN/Nikolaus

Thank you sir! I'm not getting my hopes up as I contacted 5 or 6 companies inquiring about nooglutyl over 3 months ago and never got any responses. But if I were to get my hands on this stuff it looks like it would be a good idea to use the "0.05 to about 1.2 mg/kg" dosing schedule.

For myself at 86kg I'd likely tartrate up from 4mg and beyond. Not sure if I'd go as high as the full 100mg for my body weight but let's see if I get a response from them before making too many plans.

[zeroskater6979]

Can't wait to hear of any experiences if you're fortunate enough to obtain PLR. does anyone know of any adverse SE's this drug might cause?

[Turnbuckle]

Another Hansl patent of interest--

http://patimg1.uspto...View first page

And if that doesn’t work (you need a TIFF viewer installed for patents before ’76), you can get a free pdf here--

http://ip.com/pat/US3792048

[Kahnetic]

I just left a comment on the blog asking if perhaps he simply made a mistake and was actually referring to PRL-8-53. We shall see.

[Turnbuckle]

Here's a quote from that forum--

I just happened to be browsing through this website and noticed several inquiries regarding Dr Nikolas R Hanls, early work, with PRL 8-53. You may have missed other research mentioned on this drug, in the Publication, DRUGS of the FUTURE. You can also find some of his work in chemistry journals. Dr Hanls, developed a similar compound which was hoped to be more effective than PRL 8-53, it was known as PRL 8-147. NO research is available on this compound that I know of, but was tested in rat studies at the University of Colorado, in Boulder, sometime during 1982-84. This compound may have been tested at Stanford University, but I'm not sure when this was done. The results where only considered "novel." I must tell you that the results or perhaps no results obtained, may have been due to how the rats where treated! That statement comes directly from Dr. Hanls himself!...

http://brainmeta.com...showtopic=21252

BTW, the title has letters transposed. It's PRL not PLR. PRL is the acronym for Pacific Research Laboratories

Edited by Turnbuckle, 07 August 2012 - 12:17 AM.

[Q did it!]

http://www.bocsci.com/index.asp might be a good place to get a custom synthesis of the substances. I looked through the site and could not find PRL 8-53 or PRL 8-147. Even tried CAS#s. This should be a good place to get it from if no one wants to order from China and risk getting ripped off. The company is based out of New York State, so there should be little risk if any involved in purchasing from them but more than likely the cost will be higher.

Link to their synthesis page http://www.bocsci.com/services.asp.

Custom Synthesis
The customer provides literature methods or their own synthesis route in which all details (reaction times, solvents, temperatures, analytical data, purification methods, yields, etc.) are included. If you have no technical information, we can give an estimate after we carefully review it.
Our chemists' team will evaluate synthesis and determine whether to pursue the project. We will reply you usually in 48 hours. If so, we will provide an estimate of cost and delivery time. BOC Sciences honors its quoted price even if a project requires more work than anticipated. We will charge the client only for successful syntheses.

o Custom synthesis of organic molecules in scales ranging from milligram to kilogram quantities. Those molecules include but not limit to reference compounds, starting materials, building blocks, intermediates, and derivatives of lead compounds

o Custom manufacturing of chemicals in bulk quantities

o Scale-up an existing literature or customer supplied synthesis

o Replace steps in a synthesis that do not perform well

o Design a new synthesis...

If any one does get ahold of this stuff please do report on what you find.

[Kahnetic]

The blog poster confirmed that he was in fact referring to PRL-8-53 and has now updated the post to correct his mistake. Very interesting chemical, it's a real shame how little it has been studied.

Thanks for pointing this out! Complete typo on my part, PLR: 8-53 is indeed the nootropic I was describing. I’ve changed the post to reflect that. If anyone is interested here is some more information about it: http://brainmeta.com...showtopic=20161

[CIMN]

althought this thread is about PLR. ive been wondering about RGS14, granted that you have to localy increase its levels in the visual cortex to get its memory effects, by looking at its interaction partners maybe there is a way to mimic RGS's effects by working on the chemistry on its interactions.

http://en.wikipedia.org/wiki/RGS14

RGS14 is a member of the regulator of G protein signalling family. This protein contains one RGS domain, two Raf-like Ras-binding domains (RBDs), and one GoLoco motif. The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. Acting as a GTPase activating protein (GAP), the protein increases the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.^[1]

not trying to disrupt the focus of this thread, RGS14 is another memory effecting protein.

Edited by CIMN, 07 August 2012 - 08:33 PM.

[manic_racetam]

althought this thread is about PLR. ive been wondering about RGS14, granted that you have to localy increase its levels in the visual cortex to get its memory effects, by looking at its interaction partners maybe there is a way to mimic RGS's effects by working on the chemistry on its interactions.

http://en.wikipedia.org/wiki/RGS14

RGS14 is a member of the regulator of G protein signalling family. This protein contains one RGS domain, two Raf-like Ras-binding domains (RBDs), and one GoLoco motif. The protein attenuates the signaling activity of G-proteins by binding, through its GoLoco domain, to specific types of activated, GTP-bound G alpha subunits. Acting as a GTPase activating protein (GAP), the protein increases the rate of conversion of the GTP to GDP. This hydrolysis allows the G alpha subunits to bind G beta/gamma subunit heterodimers, forming inactive G-protein heterotrimers, thereby terminating the signal. Alternate transcriptional splice variants of this gene have been observed but have not been thoroughly characterized.^[1]

not trying to disrupt the focus of this thread, RGS14 is another memory effecting protein.

Also... does the following from the wiki article imply that it also deleteriously effects learning and hippocampal based memory? Sounds like an interesting trade off and it sort of raises some questions about how memory is encoded in the first place... Is there some other function besides that of the hippocampus that can encode memory?

Increasing the expression of the RGS14 protein in the V2 secondary visual cortex of mice promotes the conversion of short-term to long-term object-recognition memory.^[2] Conversely RGS14 is enriched in CA2 pyramidal neurons and suppresses synaptic plasticity of these synapses and hippocampal-based learning and memory.^[3]

[CIMN]

Also... does the following from the wiki article imply that it also deleteriously effects learning and hippocampal based memory? Sounds like an interesting trade off and it sort of raises some questions about how memory is encoded in the first place... Is there some other function besides that of the hippocampus that can encode memory?

Increasing the expression of the RGS14 protein in the V2 secondary visual cortex of mice promotes the conversion of short-term to long-term object-recognition memory.^[2] Conversely RGS14 is enriched in CA2 pyramidal neurons and suppresses synaptic plasticity of these synapses and hippocampal-based learning and memory.^[3]

yes, its involved with learning, plasticity, the science is a bit over my head but i think its very interesting to discuss more about this protein. i dont think we should totally disregard it just because it acted as a supressor to synaptic plasticity, its known as a "key regulator" of signaling pathways linking synaptic plasticity and memory. so perhaps there is a innate inhibitory process from the brain to inhbit access plasticity as it might become detrimental to forming long term memory? i don't know but its worth a further look in my opinion. it seems it functons different in different areas of the brain so maybe it doesnt supress plasticity in the visual cortex.

http://www.ncbi.nlm....pubmed/20837545

Edited by CIMN, 07 August 2012 - 11:25 PM.

[CIMN]

sorry if i derailed the thread a bit, you guys should continue the talk on PLR 8-147 its indeed fascinating.

[Gerhard van Dieren]

Woah, surely this thread did blow up. I didn't expect this as a noot-noob, either way.. After all the digging you guys have done, what are the options for PLR 8-147?

[Izan]

I'm also very interested in this. Signed up just for this. We could contact the inventor, he is still alive and well in his eighties.

Nikolaus Hansl

Owner

Pacific Research La

7713 Pierce Street
Omaha, NE 68124-1523

Phone: (402) 391-3743

About:
Pacific Research Lab in Omaha, NE is a private company which is listed under sulfa drugs. Current estimates show this company has an annual revenue of $2.5 to 5 million and employs a staff of 5 to 9.

[Izan]

never mind, i just found out dr hansl died last november. bless his soul.

[treonsverdery]

when you view the most recent paper at pubmed, a paper on a different nootropic BMY 21502 cites the 8147 drug, bmy21502 is a racetam like molecule that improves visual task memory

Edited by treonsverdery, 09 August 2012 - 11:07 PM.

[mait]

If we have the structure of PRL 8-147 known we could ask the custom synthesis service from some Chinese company. Then after the delivery use second independent lab to test the purity and rightness of the compound obtained in first place. If the second analysis shows up ok we have a winner. I am willing to participate in this project financially as much as I can.

[Izan]

If we have the structure of PRL 8-147 known we could ask the custom synthesis service from some Chinese company. Then after the delivery use second independent lab to test the purity and rightness of the compound obtained in first place. If the second analysis shows up ok we have a winner. I am willing to participate in this project financially as much as I can.

me too! this sounds so amazing; prl 8-147 + cerebrolysin + c60 = NZT

[Q did it!]

It would probably be better to try PRL 8-53 vs. PRL 8-147. There is more information on PRL 8-53 and if i read correctly from one of the articles above it was found that PRL 8-147 may not to be very effective if at all but it could have been the way they tested the rodents were tested while on PRL 8-147. Here it is,

Here's a quote from that forum--


Quote

I just happened to be browsing through this website and noticed several inquiries regarding Dr Nikolas R Hanls, early work, with PRL 8-53. You may have missed other research mentioned on this drug, in the Publication, DRUGS of the FUTURE. You can also find some of his work in chemistry journals. Dr Hanls, developed a similar compound which was hoped to be more effective than PRL 8-53, it was known as PRL 8-147. NO research is available on this compound that I know of, but was tested in rat studies at the University of Colorado, in Boulder, sometime during 1982-84. This compound may have been tested at Stanford University, but I'm not sure when this was done. The results where only considered "novel." I must tell you that the results or perhaps no results obtained, may have been due to how the rats where treated! That statement comes directly from Dr. Hanls himself!...

http://brainmeta.com...showtopic=21252
BTW, the title has letters transposed. It's PRL not PLR. PRL is the acronym for Pacific Research Laboratories .

PRL 8-53 was tested on humans. While PRL 8-147 never left the rodent stage, based on what I have read so far on the two substances. As soon as I get the funds to gather I do plan on getting some PRL 8-53.

Edited by Q did it!, 10 August 2012 - 11:26 PM.

[mait]

Hehehe! Great success then because it seems PRL-8-53 seems to be at least on offer as chemical for custom synthesis: min order 10g for 10USD per gram (http://www.lookchem....352-87-5.html.)

Edited by mait, 11 August 2012 - 12:02 AM.

[mait]

OK! Please look up the PRL-8-53 structure (especially the lower part of it from http://www.guidechem...dic-494334.html) and compare this to amphetamine structure. Those two are in part structurally very similar by having benzene ring and amidogen components in close proximity.

Edited by mait, 11 August 2012 - 12:13 AM.

[manic_racetam]

OK! Please look up the PRL-8-53 structure (especially the lower part of it from http://www.guidechem...dic-494334.html) and compare this to amphetamine structure. Those two are in part structurally very similar by having benzene ring and amidogen components in close proximity.

So might this be illegal in the US due to the Analogue Act?

[Raza]

I'm halfway sure analogues have to be much closer in structure. And it'd have to also be a stimulant, with potency 'significantly similar' to one of the scheduled amphetamines.

[Gerhard van Dieren]

So there is no way we could synthesize this?

[Nattzor]

So there is no way we could synthesize this?

Hehehe! Great success then because it seems PRL-8-53 seems to be at least on offer as chemical for custom synthesis: min order 10g for 10USD per gram (http://www.lookchem....352-87-5.html.)

It looks like we can, someone just need to throw out $100 or a few people must go together and buy it.