LONGECITY

I'm making a seperate page for (-)-BPAP. There is a group buy going on and already eight spots have been claimed with two soon to be paid for and claimed, making a total of 10 spots already taken. I'm willing to go up to 20 spots, meaning 10 would be left if there is interest. I don't think I have to post the benefits of BPAP; but, here it is anyway:

So, I got a quote from a trusted supplier on BPAP. He can make a pure negative isomer, not racemic mixture, of (-)-BPAP. Let me remind that this compound has an inverted U-shaped curve with an optimal dose of 100 micrograms. 1 microgram = 0.001 miligram 100 microgram = .1 miligram <--Effective dose Now with 200 miligrams of this subtance it would last you about 2000 days at 100 microgram doses a day. However you would be purchasing 1G of (-)-BPAP. The supplier is making more for himself as a buisness venture and were just here to benefit from any extra he decides to make. You can guess that 1g will last a very long time.

R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane - (-)-BPAP

A chemical for brain health, nootropic potential, mood enhancement and potentially life extension, often compared with Deprenyl.


Below we present a summary of the major research results for (-)-BPAP, taken from published studies in the peer-reviewed literature. In summary:
(-)-BPAP is a powerful catecholaminergic/serotoninergic activity enhancer over 100 times as effective as deprenyl (which it was invented to replace), with a broader spectrum of neurotransmitter enhancement effects and without the negative amphetamine and MOA inhibition side effects. It has been shown to have anti-depression, neurotrophic and brain antioxidative benefits. Moreover, with a better safety profile than deprenyl, BPAP appears to have even more life extension potential than deprenyl although this last is yet untested in any mammal.

Safety, Pharmacology and Interactions

1. "(-)-Deprenyl, the only synthetic enhancer substance in clinical use is known to be a safe, well-tolerated drug. Since (-)-BPAP, ... a deprenyl-derived enhancer substance being free of the MAO-B inhibitory property ... which is ... at least 100-times more potent than (-)-deprenyl, has even a better safety margin than (-)-deprenyl, we may expect that 100-times higher doses of (-)-BPAP than the ones that exert an enhancer effect can be administered without risk of significant side-effects."R

2. "(-)-BPAP did not show any effects on spontaneous norepinephrine release. Thus, (-)-BPAP did not exert tyramine-like norepinephrine releasing action. ... Furthermore, we demonstrated that (-)-BPAP inhibited tyramine-induced norepinephrine release ... (-)-BPAP, as demonstrated here, has a similar action to (-)-deprenyl ["a blockade of (-)-deprenyl against the 'cheese effect' induced by tyramine"] concerning potential to participate in hypertensive crisis. As (-)-BPAP has an affinity to catecholamine transporters which are also carriers for tyramine, the inhibitory action of (-)-BPAP on tyramineinduced norepinephrine release may be due to its tyramine uptake inhibitory action. In the present study, (-)-BPAP was also demonstrated not to influence spontaneous dopamine release, and to reduce tyramine-induced dopamine release, as was the case for norepinephrine. Thus, (-)-BPAP inhibits the effect of tyramine."R

3. "in rats ... (-)-BPAP-14C ... was well absorbed after i.p., s.c. and oral treatment and Cmax has been reached at 30 to 60 min following drug administration. A second peak, detected at 4 hours, indicated enterohepatic circulation of the substance. The highest tissue levels ... were reached at 30 min following s.c. treatment. ... A similar distribution profile was observed in the brain regions with a peak level at 30 min. ... is preferentially eliminated through the urine, the secondary route of excretion was the stool. More than 90% of the substance was recovered in the excreta during 72 hours. The t1/2 beta was found to be 5.5 to 5.8 hours. (-)-BPAP was well absorbed and penetrated the brain. Its elimination was fast and enterohepatic circulation was observed in rats."R

4. "(-)Deprenyl (Selegiline), for the time being the only CAE [catecholaminergic activity enhancer] substance in clinical use free of the catecholamine releasing property, is metabolized to methamphetamine and amphetamine and is also a highly potent and selective MAO-B inhibitor. To get rid of these, from point of view of the CAE effect, disadvantageous properties of the compound, we synthetized [sic] in the early '90s deprenyl analogues not metabolized to amphetamines and free of the MAO inhibitory effect."

5. "Our selected reference compound, (-)-BPAP, ... a much more potent enhancer of the impulse propagation mediated release of catecholamines and serotonin in the brain than ... (-)-deprenyl ... and a compound structurally unrelated to PEA [phenylethylamine] and the amphetamines, seems to be an especially promising experimental tool for studying the nature and the physiological role of the CAE/SAE [catecholaminergic/serotoninergic activity enhancer] mechanism in the brain. ..."

6. "(-)-BPAP, obviously because of its close structural similarity to tryptamine, is a weak, selective inhibitor of MAO-A, but this effect is from pharmacological point of view not significant."R


Proven Benefits

1. In cultured rat and human cells, which "work under catecholaminergic influence", subjected to hypoxia, "(-)-BPAP and (-)-deprenyl, due to their enhancer effect, exerted a significant cytoprotective effect"R

2. "in rat mesencephalic slice cultures ... R-(-)-BPAP significantly increased the mRNA and protein levels of BDNF [brain-derived neurotrophic factor], without affecting the level of NT-3 mRNA. In addition, R-(-)-BPAP significantly increased the mRNA level of trkB [a cell receptor], but not that of p75(NTR) [another cell receptor]. These effects of R-(-)-BPAP may result in enhanced BDNF/trkB signaling, and could thus underlie the potential neurotrophic and antidepressant actions of this drug."

3. "Brain-derived neurotrophic factor (BDNF) is a member of the neurotrophin family that plays an important role in regulating survival, differentiation, and functional integrity of central neurons. BDNF interacts with a specific trkB receptor kinase and with a low-affinity receptor p75NTR. Deficiencies of neurotrophins and their receptors are regarded as an important aspect of the pathogenesis of neurodegenerative disorders. Dopaminergic neuronal death in Parkinson's disease has been associated with the depletion of neurotrophins, such as BDNF and nerve growth factor (NGF). Indeed, the levels of neurotrophins, especially BDNF, were markedly reduced in the substantia nigra of Parkinson's disease patients, in whom selective degeneration of dopaminergic neurons is evident. Therefore, pharmacological stimulation of endogenous neurotrophin synthesis is expected to become a useful therapeutic approach for Parkinson's disease. R-(-)-1-(Benzofuran-2-yl)-2-propylaminopentane [R-(-)-BPAP], a potent

4. "catecholaminergic and serotonergic activity enhancer", enhances the electric field stimulation-induced release of catecholamine and serotonin from isolated rat brain stem. Because of its "catecholaminergic and serotonergic activity enhancer" effects, R-(-)-BPAP ameliorates motor deficits in reserpine-treated rats and improves active avoidance behavior in rats under tetrabenazine-induced depression. Therefore, this drug is a promising candidate as a treatment for symptoms of depression as well as for Parkinson's disease. .... Recently, the induction of BDNF/trkB signal was implicated as an important mechanism of action of antidepressants. For example, the infusion of BDNF into the midbrain produces antidepressant-like effects in an animal model of depression. Interestingly, R-(-)-BPAP is reported to produce antidepressant-like activity in rats with tetrabenazine-induced depression. ... Our findings suggest that R-(-)-BPAP, in addition to action mediated by its "catecholaminergic and serotonergic activity enhancer" effect, may serve as a neuroprotective agent for the treatment of progressive neurodegenerative disorders."R

5. "(-)-Deprenyl, a prototype of the phenylethylamine-derived synthetic enhancer substances, stimulates the catecholaminergic neurons in the brain but is almost ineffective on the serotonergic neurons. R-(-)-1-(benzofuran-2-yl)-2-propylaminopentane, (-)-BPAP, the recently developed tryptamine-derived selective synthetic enhancer substance, is a hundred times more potent enhancer of the catecholaminergic neuronal activity than (-)-deprenyl, and is also a highly potent stimulant of the serotonergic neurons. Evaluation of the peculiar pharmacological profile, the high potency and unusual safeness and tolerability of (-)-BPAP cherish the hope that this compound by itself and in combination with uptake inhibitors may improve the effectiveness of drug therapy in major depression and diminish the number of therapy resistant cases. ... (-)-BPAP, the first tryptamine-derived selective and highly potent synthetic enhancer substance that opens a previously unknown possibility to keep the activity of the noradrenergic, dopaminergic, and serotonergic neurons in the brain on a higher activity level. ... Since (-)-deprenyl is a highly potent and selective inhibitor of MAO-B, a structure-activity relationship study was performed to develop a deprenyl-derived enhancer substance being free of the MAO-B inhibitory property, and (-)-PPAP is at present the reference substance with this pharmacological profile."R1,R2

6. "(-)-BPAP may block tyramine-induced adverse effects such as hypertensive crisis. The actions of (-)-BPAP on the spontaneous and tyramine-induced dopamine release resembled its effects on norepinephrine release. We conclude that (-)-BPAP is not only catecholaminergic and serotonergic activity enhancer, but also a norepinephrine and dopamine uptake inhibitor and a weak serotonin uptake inhibitor that does not possess a tyramine-like action on catecholamine release, and is an inhibitor of tyramine-induced release of norepinephrine. ... Based on the dopamine deficiency theory, activation of the dopaminergic system by (-)-BPAP may be useful for the improvement of motor deficits in patients with early Parkinson's disease. (-)-BPAP is also expected to improve the non-motor functional deficits such as depression that is observed in Parkinson's disease, is unresponsive to anti-Parkinsonian drugs"R

7. "in cultured mouse astrocytes ... The amounts of NGF [nerve growth factor], BDNF [brain-derived neurotrophic factor], and GDNF [glial cell line-derived neurotrophic factor] secreted from astrocytes into the culture medium increased by up to 120, two, and seven times higher than those of the control, respectively, by treatment with 0.35 mM (-)-BPAP for 24 h. ... Furthermore, the treatment with (-)-BPAP for 6 h increased the mRNA expression of NGF, BDNF, and GDNF. These results suggest that (-)-BPAP up-regulated neurotrophic factor synthesis in cultured astrocytes."R

8. "These findings suggested that a "catecholaminergic and serotoninergic activity enhancer" compound, (-)-BPAP, stimulates motor function in rats and improves motor deficits in animal models of Parkinson's disease due to its ability to induce dopamine release."R

9. "The chemical reactions between (-)-BPAP and .OH were studied ... (-)-BPAP was proved to be a good radical scavenger. It was found that every atom of the benzofuran ring, except carbon 3, was capable of easily trapping the radical, where the most active site was carbon 1 on the furan part. ... Since the single radical trapping products were still radicals, these could trap further radicals by way of cascade without any activation energy. Thus, the double radical trapping products were very stable ..."R

10. "These findings suggest that (-)-BPAP [has] unique survival activity on cortical neurons through sigma receptors."R


Potential Benefits

1. "This paper presents that a series of benzofuran derivatives prevented apoptosis induced by an endogenous neurotoxin ... it remains to be clarified whether BPAP derivatives activate transcription factors, such as NF-KB, to induce anti-apoptotic genes. In addition, the relation of the gene induction to catecholaminergic-serotonergic enhancing effects should be further examined to elucidate the mechanism behind neuroprotection by a series of BPAP derivatives."R

2. "This substance [(-)-BPAP], which is specific and hundreds of times more potent than selegiline, is now the best experimental tool to study the enhancer regulation in the mesencephalon and a promising candidate to significantly surpass the therapeutic efficiency of selegiline in depression, Parkinson’s disease, and Alzheimer’s disease."R

3. "Antiaging compounds: (-)deprenyl (selegeline) and (-)1-(benzofuran-2-yl)-2-propylaminopentane, [(-)-BPAP], a selective highly potent enhancer of the impulse propagation mediated release of catecholamine and serotonin in the brain."

4. "Hundreds of millions of people now die over the age of 80 years primarily due to twentieth century progress in hygiene, chemotherapy, and immunology. With a longer average lifespan, the need to improve quality of life during the latter decades is more compelling. "Aging--The Epidemic of the New Millenium," a recent international conference (Monte Carlo, June 17-18, 2000), showed with peculiar clarity that a safe and efficient drug strategy to slow the age-related decay of brain performance is still missing. This review summarizes the physiologic and pharmacologic arguments in favor of a peculiar lifelong prophylactic medication with reasonable chances to keep in check brain aging and decrease the precipitation of age-related neurological diseases."R


Additional Related Papers

1. "The recent discovery of the enhancer regulation in the mammalian brain brought a different perspective to the brain-organized realization of goal-oriented behavior, which is the quintessence of plastic behavioral descriptions such as drive or motivation. According to this new approach, ‘drive’ means that special endogenous enhancer substances enhance the impulse-propagation-mediated release of transmitters in a proper population of enhancersensitive neurons, and keep these neurons in the state of enhanced excitability until the goal is reached. However, to reach any goal needs the participation of the catecholaminergic machinery, the engine of the brain. We developed a method to detect the specific enhancer effect of synthetic enhancer substances [(-)-deprenyl, (-)-PPAP, (-)-BPAP] by measuring the release of transmitters from freshly isolated selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus, raphe) by the aid of HPLC with electrochemical detection. To test the validity of the working hypothesis that in any form of goal-seeking behavior the catecholaminergic and serotonergic neurons work on a higher activity level, we compared the amount of norepinephrine, dopamine, and serotonin released from selected discrete brain areas isolated from the brain of sated and food-deprived rats. Rats were deprived of food for 48 and 72 hours, respectively, and the state of excitability of their catecholaminergic and serotonergic neurons in comparison to that of sated rats was measured. We tested the orienting–searching reflex activity of the rats in a special open field, isolated thereafter selected discrete brain areas and measured the release of norepinephrine, dopamine, and serotonin from the proper tissue samples into the organ bath. The orienting–searching reflex activity of the rats increased proportionally to the time elapsed from the last feed and the amount of dopamine released from the striatum, substantia nigra and tuberculum olfactorium, that of norepinephrine released from the locus coeruleus and that of serotonin released from the raphe increased significantly in the hungry rats proportionally to the time of fasting. For example: the amount of dopamine released from the substantia nigra of sated rats (4.62 +- 0.20 nmoles/g wet weight) increased to 5.95 +- 0.37 (P < 0.05) and 10.67 +- 0.44 (P < 0.01) in rats deprived of food for 48 and 72 hours, respectively."R

2 . "In the cultured astrocytes incubated for 24 h with selegiline, the synthesis of NGF [nerve growth factor] and BDNF [brain-derived neurotrophic factor] was significantly enhanced in the concentration dependent manner, with minimum effective concentrations of 4 x 10-4 and 5 x 10-4 M, respectively. (–)-BPAP also enhanced the NGF,BDNF andGDNF synthesis, with minimum effective concentrations of 5 x 10-5, 1 x 10-5, and 1 x 10-6 M, respectively."R

3. "As (-)-BPAP is for the time being the most selective and most potent available stimulant of the enhancer-sensitive midbrain neurons, we prefer to use this compound in examining the mechanism of action of the enhancer substances. This study is an in vivo and ex vivo analysis of the characteristic dose/concentration dependency of the enhancer effect of (-)-BPAP on catecholaminergic and serotoninergic neurons."R




Although the owners of this website (Paul and Kitty Antonik Wakfer) assert that, except where indicated, they are the creators and originators of its content, and also assert that they should receive value commensurate with that which anyone reading it receives from the information on it (see http://morelife.org/supporting.html for elucidation of the notion of value-for-value), the site content is not 'copyright' as that term is legally defined because its creators do not agree with government copyright laws.

Readers are welcome to copy and distribute any text within the site as long as they do not modify the text and they provide a link to this website as its source, so that those who read it will know where Value for Value gained, can be returned. If those who copy text from or link to this website, in the manner just described, gain value from that action, then they are similarly expected to return some of that value to its creators. Those who make use of any text on this website in any other manner than as described in this paragraph without explicit permission from its creators will be socially preferenced against

Detailed paper about BPAP.
http://onlinelibrary...bjp.0702995/pdf
Summary of finding in pictorial form:






Edited by yadayada, 29 May 2013 - 05:00 AM.

If interested then just PM me. I will wait a longer with collecting any more funds.

To confirm, I have agreed to manage the UK / EU DISTRIBUTION

To confirm, I have agreed to manage the UK / EU DISTRIBUTION

Thanks. Appreciate that.

I normally read these forums for the entertainment; generally, very few of the novel substances this board decides to investigate for human use pose a high risk of acute toxicity. I'm not here to lecture, in the end what one decides to ingest is one's own prerogative. Still, I saw this compound mentioned on the nootropics subreddit and that there was a group buy on Longecity, so I figured I should post here. As I said, I'm not here to lecture, but here are my two cents on the issue:

It is a terrible idea to ingest this compound and you have referenced the reason why in the initial post. To begin, the first study reference is in regards to the safety of the primary pharmacological target and (-)BPAP’s MAOI properties, or lack thereof. As far as toxicity is concerned, it is unlikely that this drug’s primary mechanism of action (CAE/SAE effect) would contribute to any toxicological profile this compound has. While there are certainly inherent risks in altering monoamine levels and release of monoamines from the synapse, that is not what really concerns me about this compound.

The most concerning aspect of this drug is that it is shown to enter enterohepatic circulation in rat models of pharmacokinetics. This is extremely worrisome for a compound with so little toxicological data in the literature. What this means, essentially, is that there is a good chance that concentrations of (-)BPAP in the liver will reach extremely high levels; levels that would be considered supraphysiological in any other parts of the body. The implications of this are obvious – there is a chance that (-)BPAP exhibits hepatotoxicity at such high concentrations, which could lead to liver damage and/or liver failure.

Additionally, I’d like to ask a question just for the sake of contemplation. Why would a rockstar pharmaceutical chemist such a Joseph Knoll - known for his discovery of Selegiline - be unable to bring a close relative of Selegiline to a pharmaceutical company for further development? This is especially true given the bold statements he makes in his paper and its blockbuster potential in the treatment of Parkinson’s and Alzheimer’s. My personal guess would be that while the drug looked very promising due to its mechanism of action and selectivity for monoamine release upon stimulation, it’s pharmacokinetic and pharmacodynamic profiles were subpar. Perhaps a novel derivative of (-)BPAP was developed with an improved pharmacological profile, or perhaps research into that particular subset of CAE/SAE selective compounds was abandoned for more promising ones.

Either way, in the end everyone will make their own choice and choose to do whatever it is they want. I would implore anyone considering this compound to wait for the next exciting drug with a better looking safety profile, but it all boils down to personal choice. Good luck to everyone, and for those that do choose to try the compound be sure to keep us updated.

Edit: Too lazy to proofread. Cut my grammar and repetitive word choice some slack and focus on the main points, if you will.
Edited by mugatu9000, 29 May 2013 - 07:29 PM.

Just as a reminder, [(-)-BPAP] is for research purposes. I do not advocate the use of this, [(-)-BPAP], compound nor do promote it. Having said that, this compound has been trialed and tested by members of LEF back in 2005. The creator of the "morelife.org" website (Paul Wakfer) has continuously consumed BPAP for, I believe, a year. I can't speak for him; but, I think he has performed checkups on his liver throughout that time. I should also note that he has abandoned taking BPAP for similar reasons mentioned here. Having not enough research done on safety and toxicology profile. Just thowing this out there.
Edited by yadayada, 29 May 2013 - 09:35 PM.

I just noticed that according his regimen BPAP was again added to his regimen. Worth asking him about how it's working out.

Yadayada,

This is really looking interesting. I PMed you about a portion of -BPAP for research purposes. Very nice that you are doing this.

how would you measure .1 milligrams? or even handle such a small amount.

how would you measure .1 milligrams? or even handle such a small amount.

never mind just saw there other thread

Edit: please feel free to delete this post, I now see a previous poster had the same question, and I do not wish to clog up the thread.
Edited by Godof Smallthings, 30 May 2013 - 04:33 AM.

The most concerning aspect of this drug is that it is shown to enter enterohepatic circulation in rat models of pharmacokinetics... What this means, essentially, is that there is a good chance that concentrations of (-)BPAP in the liver will reach extremely high levels; levels that would be considered supraphysiological in any other parts of the body. The implications of this are obvious – there is a chance that (-)BPAP exhibits hepatotoxicity at such high concentrations, which could lead to liver damage and/or liver failure...

Any information relating to POTENTIAL TOXICITY is extremely valuable and hence thank you for this... Personally, I am very fond of my LAB RAT and would most certainly not wish for any harm to happen to him

However, I think we need to be careful here not to 'throw the baby out with the bathwater' so to speak; in that if this is the only concern then it is easily addressed by carrying out regular LIVER FUNCTION tests on one's LAB RAT; and adjust the dosing schedule accordingly.

Is there any other salient concern that you have regards the potential for toxicity other than this?

Someone sent a payment; but, forgot to include his address. Please PM me with your address whose last name ends with an *n and payed 2 hours ago. Thanks.

Have some room for last minute participants. Everything should be done by the end of this month.

You can PM me if you still want to reserve a spot.

OK, I'm about to close this group buy. In two weeks the compound should be ready and by then it should take a week or two to have (-)-BPAP in your hands. I have room for a couple more participants if they want to join.Serious ppl only. PM me if you want to join.

After I close the group buy on this Ill start the IDRA-21 group buy.

Thanks man. You're awesome for organizing these group buys.

<------------WANTS!

Willing to shell out under 50 $ us for a years supply.

im willing to split a portion with some one, 50/50 or so if any esteemed fellow wants after they receive order.

While I sadly can't participate right now, I would also be willing to buy a share of someone once you guys receive your orders. Really curious about the first results in a few weeks

OK, group buy is closed. Thanks. Everyone who is in the group will recieve the compound by the first or second week of July. Please don't hold my word, as sometimes ETA varies with custom synthesis'. Thanks. Glad you guys and gals could be part of these exciting times.

Just to be on the safe side I'll begin the IDRA-21 group buy once everyone in this group buy has (-)-BPAP in his/her hand.

OK, group buy is closed. Thanks. Everyone who is in the group will recieve the compound by the first or second week of July. Please don't hold my word, as sometimes ETA varies with custom synthesis'. Thanks. Glad you guys and gals could be part of these exciting times.

Just to be on the safe side I'll begin the IDRA-21 group buy once everyone in this group buy has (-)-BPAP in his/her hand.

It's a shame that I missed this group buy, but please count me in in the IDRA-21 group buy.

Regards

lol, nice avatar! Sure thing.

You're a star yada

While I sadly can't participate right now, I would also be willing to buy a share of someone once you guys receive your orders. Really curious about the first results in a few weeks

The same goes with me.

You're a star yada

Thanks. Only worrying about the taxman with these funds from overseas under my name. Hmm..

You're a star yada

Thanks. Only worrying about the taxman with these funds from overseas under my name. Hmm..

Looked at this in PayPal website. i dont know if this will affect you but you are not taking payments for 'goods or services', but you are only acting as an intermediary between seller and several buyers. I suspect you may still be contacted if you receive more than 200 payments in year. i would think that the rule applies for 2013-14 too.

• What is Internal Revenue Code (IRC) Section 6050W?
  
  
  Under the legislation, we'll report to the IRS the total payment volume received by US account holders whose payments exceed both of these levels in a calendar year:
  
  • US$20,000 in gross payment volume from sales of goods or services in a single year
  • 200 separate payments for goods or services in the same year
  IRC Section 6050W applies to all payment processors, including PayPal. Our goal is to help PayPal sellers understand and comply with the new requirements.
• How will I know if IRC Section 6050W affects me?
  
  PayPal will track the payment volume of your account(s) to check whether your payment volume exceeds both of these levels in a calendar year:
  
  • $20,000 USD in gross payment volume from sales of goods or services in a single year
  • 200 payments for goods or services in the same year
  You may be asked to add your tax ID number, such as a Social Security Number (SSN) or Employer Identification Number (EIN), to your existing account(s), if you don’t already have one on file.
  If you cross the IRS thresholds in 2012, PayPal will send Form 1099-K to you and the IRS for the 2012 tax year in early 2013.

Edited by autopilot, 19 June 2013 - 10:51 AM.

Hi, one member just dissapeared and I was not able to contact them. I think they are having some trouble with the law or something and I don't want to endanger myself or my supplier. That leaves me with one spot left since I refunded that amount and am ordering a quantity that includes that payment. So, if you didn't make it in time to get into this group buy, this is your chance. PM me if you're interested.

Did this group buy in ever go? I would be interested in hearing how everyone's research is going.

Final steps are being completed. Purification, etc. Results should be in in some time.

Final steps are being completed. Purification, etc. Results should be in in some time.

I was under the impression the synthesis was only just about to begin. Again, thanks for putting all this together yadayada and scienceguy.

how many days does it take for synthesis