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
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Detailed paper about BPAP.
http://onlinelibrary...bjp.0702995/pdf
Summary of finding in pictorial form:
Edited by yadayada, 29 May 2013 - 05:00 AM.
