I'm thinking of taking PRL-8-53. Very intrigued by this and am wondering why studies on this were seemingly abruptly stopped in the late 70's? Here is an article I found on it:
I suspect studies were aborted for good reason; it was likely found to be less effective than the first studies indicated. There is no other reason why it would be abandoned, if it was truly as effective as the preliminary studies indicated, pharma companies would have leapt on it. As it is no one even bothered patenting it as far as I can tell (perhaps the original researcher owns the patent, but I don't believe any pharmaceutical companies own it).
With all due respect Box, I cant necessarily agree, as Id hardly call it ineffective by any means. PRL is a pretty novel substance, and the idea of bringing nootropics to market is still nothing more than a vague dream at the time, let alone back when those studies were taking place. A general lack of interest is certainly a possibility here. Interested as you and I may be, I hardly think the average scientist back then would care so much for the idea of chemically improving his or her intelligence. It sounds a bit naïve, and there certainly were individuals involved in this field at the time with a great interest in nootropics, but it simply wasnt all that important in the grand scheme of things. Only now are we starting to realize the importance of cognitive enhancers, and the profound ways in which they can affect the mind, yet even today, weve only scratched the surface of whats possible out there. From the looks of it, the termination of the studies seemed to have more to do with PR issues between the patent holder and the university (There was a lawsuit case between the two, which Dr. Hansl, the patent-holder, lost the case. Not to even get into the financial problems pertaining to these studies, this fact alone would certainly hinder any further progress. I for one would consider these issues more relevant in the studies' termination than a lack of effectiveness. However, to contradict myself and support your point somewhat, PRLs biggest drawback is without a doubt the incredibly fast-building tolerance. This could have almost certainly been grounds for keeping it off the market, effective as it may be. As far as my personal experiences go, it's not the end-all, be-all of the nootropics realm (and lets be honest, nothing will be), but I do find PRL quite effective in fulfilling the (somewhat) limited role it plays in my stack. PRL keeps me awake better than amphetamines (and even better with the combination of the two), significantly improves digit retention, working memory, muscle memory, and long-term memory. Moderate increases in short-term memory are observed, hand-eye coordination is god-like (probably the most pronounced effect for me overall), and my focus and concentration are improved, as with all other dopamine agonists. It combines wonderfully at a dose of 10mg with 30mg Coluracetam, 20mg Dextroamphetamine, 250mcg Clonazepam, 900mg Krill Oil, 60mcg Methylene Blue, 2g Piracetam, and 4mg Intuniv (yes, all at once :D ).
A bit of a stupid question I suppose, but I'll ask it anyways since, presumably, it shouldn't be too difficult to answer. In fact, if I'm honest, I've probably answered this myself already. If anything though, I hope someone can confirm my understanding here.
So, I understand that PRL 8-53 is a dopamine agonist, along with its Histamine 3 inverse agonism and a host of other unknown MoAs. Now, it was mentioned that it potentiates the dopaminergic effects of other substances. However, it was also mentioned that PRL 8-53 *does not* potentiate the effects of amphetamines, but it only mentioned that in relation to its actions on serotonin and norepinephrine, ignoring dopamine altogether. Now, you can certainly tell where this is going, and why I labeled it as a "stupid" question. So, being that dopamine was not mentioned with regards to potentiation, I extrapolated that the dopaminergic effects of amphetamines are in fact potentiated by this substance, but without having seen this confirmed in the paper, I cant say definitively if this is true. Now, this may have been mentioned in the full study, but I only have access to the abstract and what I recall of the many PRL-related discussions on the web, here on Longecity as well as over on Reddit and a host of other sources, so that's what I'm basing my understanding on at the moment. Now, it's a bit embarrassing that I'd even be asking this, but I'm certainly far from a pharmacologist, just an individual with a strong curiosity for a plethora of topics, pharmacology/neurology-related or otherwise. Blame the Aspergers, haha. Now, I assume I'm right on this point, but there's certainly a chance I could be wrong. So, just for the sake of confirmation: correct or incorrect?
It feels a bit incomplete at times being a part of this community without a decent pharmacological knowledge base. I certainly should be spending a good portion of my time studying this topic, as I feel quite inexperienced. Still, I suppose my anecdotal contributions could be of use to many in this community. I digress
One major problem with PRL 8-53 Ive always had is tolerance. Ive been incredibly paranoid of building up tolerance, so Ive restricted my use to a maximum of 3 times a week spaced out, usually only 1 or 2 doses maximum. Is this a good rationale, or would I be fine in dosing more frequently without risk of tolerance? I adore this substance, and its done quite a lot for me, so I couldnt imagine what might happen if it stopped working as well for me as it does now. Has anyone figured out a way to reduce, slow, or better yet prevent tolerance? Im already using MXE at holing doses once a week to help reset tolerance. So far, having used PRL 8-53 since October of last year, Ive never run into any issues with tolerance. Any tips on avoiding this?
Also, a bit of a crazy thought: PRL 8-53 is always incredibly numbing to the tongue. Does it work as a topical anesthetic like cocaine, by any chance? Has anyone tried rubbing the powder on their skin to test this? Maybe Im just insane for suggesting something like that, but I genuinely do think its a possibility. Of course, I dont have much of a supply to waste, but for those that do, a simple test like this would take about 15 seconds, maybe a bit longer. Not too bad, huh? And no, I dont have any evidence, just a hunch.
On another mildly off-topic note, I'm still very interested in testing PRL 8-53s younger brother, PRL 8-147, assuming we can ever manage to obtain the chemical formula and succeed in convincing a company to synthesize the compound and another, hopefully NSN, to make it available for purchase by the general public (multiple big-ass warning labels would be warranted, in this case). Now, it's very important to mention that the only testing ever to take place with this compound was on rats, as most of you already know, so it's definitely not something for the faint of heart, and testers should take great pains in ensuring testing is gone about in as safe a manner as possible, if at all, and I certainly wouldnt blame anyone for not wanting to ingest a substance thats never once been tested in humans. That no further tests took place is probably, once again, a byproduct of all the events taking place with Dr. Hansl and the lawsuit situation. A shame, as this was certainly one promising substance, for what little information surrounded it, and even in its seeming demise, its still near the top of my must-try list of substances. Going back to PRL 8-147 itself, caution is of the utmost importance if is to be tested by any of us, not only for our own sakes, but also for the sake of potential future testers, who would almost certainly be gravely disappointed to see this compound receive negative attention due to negligence on part of the testers, which could easily lead to the scheduling of said substance. Equally important are the observers, especially those in a position to see this substance banned, whether that decision is reached through direct or indirect influence on part of that observer. To avoid this from happening, inform yourself, apply yourself and the information at hand to maximize safety and minimize harmful and dangerous effects, and take full responsibility with yourself, only pushing forward if you are comfortable and capable of doing so. If it isn't possible to practice safety in the most ideal manner, then testing should not take place. This compound, and furthermore any compound with unknown effects and/or a potentially sketchy safety profile, should be treated as if it were a psychedelic trip taking place in a first-time user. Restrict movement and action only until you can be sure what type of activity can be considered safe, dedicate yourself to focused activities relevant to the effects of the substance itself in order to take full advantage of the experience of ingesting a novel substance, and most importantly, make sure a responsible, adequately educated and informed, and most of all trustworthy sober sitter is on hand at all times, in case anything goes wrong. Avoid any sharp objects, anything that could be used as a weapon, and anything that you could fall on if dizzy or imbalanced, should any unpredictable effects pop up. Prepare everything beforehand, any food and the like, activities you'll be doing throughout the duration of effects, if any, and any possible missteps that could take place during the experience, Foreshadowing and being prepared for the worst does not make one a pessimist. Theres always that possibility worse could come to worst, likely or not, and to prepare for the unlikely is every bit as important as preparing for the guaranteed. Keep usage of other substances to a minimum if possible, to ensure no dangerous interactions take place. The more substances added, the more unpredictable the experience becomes. Overboard as it may seem, its always better to be safe than sorry. If minimizing use of other substances is not a possibility, once again, save the testing for another time. Your health is more important than your pride or ego, or your excitement and anxiousness to try a new substance for the first time. Don't let eagerness get in the way of safety. That's what causes individuals to harm themselves, permanently damage themselves, or even kill themselves - keep this in mind. Do not fear, but tread carefully and keep a clear mind. Always assess your judgment thoroughly, and if you're not in a state to have this experience, don't. As the nootropics scene continues to progress, so too does the risk factor with each of the substances we test. It can very realistically happen that C16 become a scheduled substance as many of us are aware, and there's no reason not to exercise similar if not greater caution in the case of PRL 8-147 in avoiding this scenario of even more excessive prohibition. With each passing day, yet another nootropic substance emerges from the thick, and so too does the information surrounding it, oftentimes almost deliberately vague, yet the potency of each new compound find itself even greater than the last. Higher potencies almost definitively can be extrapolated to result in an increased risk factor, so safety absolutely comes first here, above even scientific progress. There's no sense in testing a compound if your lack of preparedness, an improper mental state or some other hypothetical scenario will likely result in overwhelming consequences. The long-term halting of progress is never worth any short-term progression, however revolutionary that may be. Save the tests for an ideal time and place, for that is where the risk-reward factor is most favourable for us all, as well as where the most progress can be made and the most useful information obtained. More potent related compounds cannot be said to guarantee increased danger (especially if an additional MoA results in improved safety; hypothetically, an amphetamine that acts to increase BDNF expression, to block NMDA, and to agonize AMPA would, despite potential neurotoxicity from the combined dopamine and AMPA agonism, not be neurotoxic at all due to the addition of NMDA antagonism and increased BDNF expression. Of course, this would depend on the extent said substance acted on those receptors, but thats beside the point. The point is, such a substance could be possible, at least in theory. In reality, though, I know of no single substance that uses one mechanism of action to protect from damage of the other. If anyone can show me otherwise, Id love to see an example.), but it doesn't hurt to be careful and to inform oneself as thoroughly as possible. I can't say it enough - don't be an idiot, and *never* go into this with your eyes closed, and, more importantly, your mind.
Now that that's over with, I suppose I should finally get to the point I was intending to get down to in the first place: a member on Reddit managed to get into contact with one of Dr. Hansl's relatives 7 months back, but we haven't heard from him since. This could mean nothing came of his efforts, though as far as I'm aware, his reasoning for getting in contact with this relative was for discussing PRL 8-53 and raising awareness of the returning interest in this compound, not to obtain any information on PRL 8-147. This could mean the individual on Reddit was simply busy and either could not update us on his assumed progress or forgot about this topic and decided to move on to other things, which is completely understandable. Either way, I want to be sure at the very least whether or not we can achieve anything here, and I'm optimistic and intuitively hopeful we will. If anyone's still interested in the testing or at least in receiving more information about this compound, and I may just do this myself when I have the time and if I have the means - it would be of great help to this community to get into contact with this relative, should anyone find out how to seek her out, and I ask that anyone who is willing takes the time to get in contact with this woman. She may know the chemical formula for this substance, and if this is the case, she is able to give it to us as well. Whether or not she's willing to do this tremendous favour, seemingly simple as it may be to fulfill, is entirely a different story, and I wouldn't blame her being that we're hardly more than random strangers scouring the internet looking for random tidbits of information so as not to bore ourselves to death in her eyes, though that's a very cynical way of looking at things, and possibly just a bit inaccurate (Just a bit
). From what little impressions I get from this individual and of her character, based entirely on her conversing with this Redditor and his few comments of her, she does seem to be a very kind, sincere lady, and I have no reason to believe she wouldn't be more than willing to help out here, so long as we dont come off as demanding or rude. If no one else expresses interest, I'll take it upon myself to contact this individual, as soon as I have the time and as soon as I obtain the means of finding her contact information. Going through Dr. Hansl's obituary and finding this relative through Ancestry, if such a thing can realistically be done, would probably be the best way to get in contact with this woman. I've not used Ancestry more than once myself, and I'm unsure if searching for specific information on relatives is at all possible or allowed in the case of non-relatives or any individual at all for that matter, but in my limited understanding, any individual can research information on any person in the world, relative or not, so long as they have a paid account. I know what some of you are going to say, but hey, it's not stalking if we have a good reason to be doing this and aren't going around harassing anyone, especially the potential benefactor. I say we go for this, being that it's quite possibly our only chance to eventually get ahold of and begin testing on PRL 8-147. I will attempt to go about this process in as professional a manner as possible, and I'll do my best to ensure no one is harmed in this testing process by properly informing those who wish to join me in this cause to the best of my abilities, as well as empowering said individuals to inform themselves through whatever means available to them, and I shall of course do the same myself. Of course, this is all assuming I succeed in obtaining the information I seek and in putting it to use, but once again, I'm quite optimistic this "operation," so to speak, will be more than successful, but it will take time, and likely quite a bit of it. I ask that those ready and willing dedicate themselves to make as much effort as necessary to get this done. We could use an effective communicator on these boards to present a nice, honest (maybe not such a good idea) argument as to why it would be in the best interests of both parties to give this information away. If such a person cannot be found, I will once again take on this responsibility myself. Thanks to all of you for taking the time to read this long, drawn-out post, and I sincerely hope something good comes out of this, and that, through this hopefully positive outcome, we may continue to progress in the nootropics realm without drawing unwanted attention to ourselves through reckless, irresponsible behaviour and actions. As always, stay safe, maintain personal responsibility in realizing your ownership of your own actions, especially if you intend to do the same as myself and test these novel substances in the future. I know I said it earlier in some sense, but Ill say it again for the sake of beating it into your thick skulls, be constantly aware at all times and inform yourself as best you can - no, better, and most of all, don't do anything reckless or stupid. We dont need any deaths on our hands in the process of testing novel substances. Hell, we dont need a broken ankle. Cautiously, slowly, and with plenty of forethought, yet maintaining a constant, passive vigilance thats the only way to go about exploring the unexplored without getting yourself harmed.
Good luck, Longecity. I'm ever so eager to see and realize the incredible things we'll be achieving in the future. C60, Methylene Blue, IDRA-21, Coluracetam, PRL 8-53...even now, we have so many substances within our reach that are infinitely interesting, and day-by-day we continue to improve, coming up with yet more effective substances. I can't imagine where we'll be 10 years from now and, to contradict a bit of what I've just said, I simply cannot wait. As much as I try to exercise patience, I can't help but get incredibly giddy for what awaits just around the corner. My impatience is killing me, but I always think forward and look at what were doing, and I just couldnt bear to experience that so quickly, so I started thinking again and decided Im just going to take it slow, wait for these amazing substances to show what theyre capable of. Sometimes, I feel as if theres too much to look forward to, and no time to cherish that anticipation. We live in a wonderful generation to be able to bear witness to achievements so great as these. Are you ready to take on the next challenge, my friends? Let us hope so, and I wish you all a wonderful day. Maintain good vibes in this community, for it is unimaginably important that we remain both positive and perpetually aware of our surroundings in our journey through the depths of cognition, of human consciousness, of immortality. And together we journey across the stars, aimless but with our intentions clear as day and our mind always open to discovering the new possibilities that patiently await us at that final destination, wherever that is. We sit hand-in-hand, dedicated to the causes that drive us forward - the elimination of aging and more broadly, all disease, the maximization of enjoyment and fulfillment in life, the realization and practice of humility and generosity, the achieving of an egoless, efficient way of thinking, the realization of the ultimate in nootropical (new word, write it down folks!) vision, the elimination of war, corruption, greed, and the release of our incessant need to control everything but ourselves, even our own situations allowed to be as they are, untouched by a single human soul. And thus, life is that much closer to perfection. That is where we are headed. Of great importance to understand is that everything in life is a great paradox. Forcing one's way along seems the best path to progress, the best method in fulfilling this goal, but this is not the case at all. In understanding the great paradox of life, we become free of these animalistic tendencies, of these counterproductive, secretly illusive needs that bind us in unbreakable chains. All is not lost in the pushing aside of the ego for a greater cause. In fact, through the application of this tremendously positive change in mindset, it becomes possible to realize all progress conceivable. Indeed, the answers lie within our own minds. They are directly in front of us, as they have always been, but through our constant negative thought patterns, it becomes invisible. For all of us, set aside these notions you cling so tightly to and think in a new light. If every person that reads this takes it to heart and mind, we may just reverse the self-destructive patterns that have plagued our existence since our very conception. The elimination of negativity is quite realistic so long as we collectively work towards that goal. So I ask every last one of, again - take all of my words to heart and mind and use them to actively change your condition, your personal situation. Nothing lasts, but all is not lost in the process. Free yourself of counterproductive habits. Think in a way that betters *you.* Frame your situation to create an advantageous outcome for you and for all. You can live as you dream to live. Nothing comes free, so for the sake of the betterment of humanity, start working today.
Edited by Ekscentra, 23 June 2014 - 09:12 PM.
![PRL-8-53, dopamine agonist or not? [speculation] - last post by Keizo](https://www.longecity.org/forum/uploads/profile/photo-thumb-31592.jpg?_r=1403204609)
