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Centrophenoxine


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#1 xanadu

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Posted 08 August 2005 - 07:20 PM


I've read the research, or at least what is here and some on the web. It's supposed to improve brain metabolism, improve use of choline, improve mental functioning and is an antioxidant. One of the more interesting claims is that it removes cellular "garbage" and reverses age related decline. This supposedly happens in all our cells with use of centro, not just our brains. Is it true that this junk that collects in our cells is in part reponsible for aging? If so, then centro might be an anti aging compound as well as a brain stimulant. I haven't seen any claims that it extends life.

Can anyone give their results with this drug? What were the short term effects and the longer term effects? I know it will be subjective but that's important info too. Does it produce insomnia? Do the stimulant effects carry over into motivation, physical activity, concentration or what? How would you compare it to piracetam, for example?

Does anyone know about the lipofuscin removal and how significant that is? All I saw were short term studies on rats. What about long term studies on humans? Do these benefits continue after centro treatment was stopped? Did the rats live longer on it than without? It sounds like the best thing since the invention of the wheel but I wonder what benefits it really gives and what are the drawbacks? I have some that I bought but haven't tried yet. It may be too stimulating and keep me up at night. What doses do those of you who use it take? I've heard from 200mg to 500gm per day.

#2 Guest_da_sense_*

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Posted 08 August 2005 - 08:46 PM

I take about 100 mg per day (since i also take AGPC which boost acetylcholine). Since i've started using it i didn't notice any effects. Probably the dose is too small, but it take it for it's benefits not effects.

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#3 lemon

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Posted 08 August 2005 - 10:13 PM

I take 300mg with piracetam. It's slightly stimulating at that dosage (atleast for me).

#4 wannafulfill

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Posted 08 August 2005 - 11:46 PM

An easy way to see if it is too stimulating is to take it morning only and to titrate up from a small starting dose.

Edited by wannafulfill, 09 August 2005 - 04:44 AM.


#5 enigma

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Posted 09 August 2005 - 06:09 AM

Can anyone give their results with this drug? What were the short term effects and the longer term effects?


Throughout all of last year I took DMAE, and for the last month or so I have been taking Centrophenoxine, they seem to exhibit similar effects with no noticeable difference.

I definitley notice a focus increase, and there is probably a learning improvement aswell. It seems I get more done when taking it, I suspect there is a subtle direct effect on goal orientated motivation. There is a study talked about on the VRP website that lists increased motivation and initiative as some of the effects DMAE had in some elderly patients. Also, on bulk nutrition there is a few reviews (one of them mine) that list increased motivation and a focus increase from DMAE use.

Basically, throughout most of high school my grades were poor, I did next to no work and lacked focus very badly. And then, in my final year of school (the only one that counts for university placement in this country) I found myself better able to focus, learn and more driven. So, I did pretty well, for the first time and in hindsight, I think this may have been largley due to DMAE which I took through that whole year. However, I didnt really think that this was due to the DMAE at the time, but rather due to some sort of natural change in myself. I didnt know much about DMAE when I had taken it initially. After one year of use I stopped taking it because I had become immune to the stimulant effect (which was always mild).

So, this year I began university without DMAE, once again lacking focus and the will to work very badly, which caused me to rarely turn up and do very little work. However, I didnt attribute this to DMAE because until recently I didnt know much about it. Towards the end of semester I started taking it again, and was able to function better I think.

Now, on Centrophenoxine, once again I am able to focus better, its effect is subtle and hard to pick up on (other than the stimulant effect which I dont get anymore) but it is there.

Also, I have not noticed any insomnia from Centrophenoxine or DMAE.

And, as for lipofuscin, this is an excerpt from the article on Centrophenoxine by James South.

"Animal studies have shown centrophenoxine to be highly efficient at removing this cellular garbage- notable reductions in mice occur within 6 weeks. One study with aged rats found a 28-42% reduction in brain lipofuscin levels after 8 weeks of centrophenoxine treatment."

How would you compare it to piracetam


DMAE/Centrophenoxine I suspect to enhance memory, focus, motivation to a small extent and also mental energy.

Piracetam is not really very comparable IMO, piracetam seems to improve language ability where DMAE does not obviously. Piracetam also has a stronger long term memory improving effect. If I take piracetam without centrophenoxine, I suspect my focus suffers slightly, something I have noticed on the road.
Centrophenoxine does not obviously make me smarter, or a better thinker, where the racetams do.

#6 johnmk

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Posted 09 August 2005 - 12:26 PM

How does one cap centrophenoxine? I ordered some and it's rather . . . clumpy.

#7 johnthornton

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Posted 09 August 2005 - 03:19 PM

enigma - what's your dosage of centrophenoxine?

#8 xanadu

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Posted 09 August 2005 - 05:25 PM

Yeah, I noticed the clumpyness too, johnmk. I crushed it up with my fingers but haven't capped it or tried it yet. It sounds interesting, good report, enigma. I'm still dealing with the stimulant effect of piracetam and hesitate to take on more stimulus with the centro. I have noticed a lack of motivation in the last few years, laziness really. It would be nice to get more done.

If the cellular garbage is from aging and centro gets rid of it, wouldn't that reverse aging to some extent? Seems logical unless the garbage does no harm. If it had made the rats live longer we'd have heard about it. That aspect is either under researched or means little. DMAE is supposed to improve choline use and centro is supposed to get dmae into the brain better. If it was't for the stimulant effect I'd try it right now.

Is gaba a good thing for calming you down and making you sleepy? What about long term use?

#9 Guest_da_sense_*

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Posted 09 August 2005 - 08:44 PM

xanadu i've tried doses of gaba up to 5 gr. it never made me sleepy, and in doses higher thatn 2 gr it gave me nausea (i usually rarely have nausea from anything), and i think i feel little drowsy in the morning after...personally i wouldn't recommend gaba
i'm waiting for some theanine to try, should be better by what other say

#10 catdaddy

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Posted 09 August 2005 - 08:59 PM

xanadu- My personal experience with gaba has been benign- I occasionally take 2-5 grams before bed. 5-10 minutes later I get a warm, pleasant full body flush(vaguely similar to a niacin flush, but soothing rather than uncomfortable). After a few minutes this subsides and I make my way to dreamland.
So check it out. It may or may not be something that works for you, but I like it.

#11 treonsverdery

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Posted 10 August 2005 - 03:57 AM

If it had made the rats live longer we'd have heard about it

There is a pubmed abstract with rats or mice living 3/10 longer

#12 xanadu

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Posted 10 August 2005 - 06:01 PM

treonsverdery wrote:

"There is a pubmed abstract with rats or mice living 3/10 longer"

That's very interesting, I hadn't heard that. Do you mean 30% longer? I wonder why we haven't heard more about this? I've heard a fair amount about food deprivation leading to better health and longer life. That is very hard to maintain with humans and would require a fanatical degree of willpower to achieve. Even getting down to normal weight is hard for most people. If centro can do the same thing (life extention) just by popping a pill, that would be very nice, wouldn't it? When something sounds too good to be true, it usually isn't true. That's why I have some scepticism about it. Seems like there would be more buzz over it if it really worked that well. But, since it's been researched for a number of years it would seem to be safe at least. The other benefits sound good enough to make it worth it. The anti aging properties would be a nice bonus if it really does that. Years from now they might be wondering why people were spending so much money on viagra when life extention drugs were freely available.

catdaddy, I tried some gaba last night and it seemed ok. I used it instead of phenibut and it worked about as well. I took just under 2gm and felt a trace of stomach awareness. Not really nausea but close to it. Gaba is supposed to be good for your skin and has other benefits. Do the sleep inducing effects wear off if you use it often?

I seem to be getting used to the piracetam though I can still feel the difference. I may go to centro soon. I seem to react to smaller doses than most so I will try a small amount, perhaps 250mg a day to start. I will report back if I begin to get younger. Or maybe I should keep that quiet so the price doesn't go up? Join the conspiracy, as it were.

#13 xanadu

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Posted 11 August 2005 - 11:29 PM

I read that after an 8 week period the rats had lost a high percentage of the "garbage" in their cells. Since it takes many years to collect and can be gotten rid of in a short time, perhaps it would be good to take centro for a couple months a year and then lay off it? Have there been studies on long term use of centro? Does anyone have links to it?

#14 scottl

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Posted 12 August 2005 - 12:06 AM

http://www.imminst.o...&f=199&t=387&s=

with all the other research LifeMirage was nice enough to gather.

#15 xanadu

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Posted 12 August 2005 - 12:18 AM

Yes, thank you, Scott. However, as I said in the first post, I've already read the info you linked to. None of that is long term and when they do mention periods of time it seems to be 2 to 3 months. My question is, if it removes the garbage in 2 or 3 months and reinvigorates the enzyme machinery then would it be good to take it year around or would it be better or just as good to take it for 2-3 months and then lay off for a year or so? This goes back to the question of should we lay off noots now and then.

#16 rshack

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Posted 12 August 2005 - 08:15 PM

Here's a short article that summarizes what is known about this drug. It looks interesting. Keep in mind that in many cases the rodents models that show a dramatic increase in life span are strains of rodents selected for a short life span and therefore very, very high chronic oxidative stress and poor DNA repair. These experiments do not indicate that the same would occur in humans taking any drug.


Pharmacological Interventions against Aging through the Cell Plasma Membrane
A Review of the Experimental Results Obtained in Animals and Humans
Ann. N.Y. Acad. Sci. 959: 308-320 (2002).

ABSTRACT

As was shown in a recent review by this author (Ann. N.Y. Acad. Sci., 928: 187-199, 2001), oxyradicals cannot be considered only as harmful by-products of the oxidative metabolism, but living cells and organisms implicitly require their production. This idea is supported by numerous facts and arguments, the most important of which is that the complete inhibition of the oxyradical production by KCN (or by any block of respiration) kills the living organisms long before the energy reserves would be exhausted. This new theoretical approach not only helps our understanding of the normal functions of the living organisms, such as the basic memory mechanisms in the brain cells, but also helps in identifying the site-specific, radical-induced damaging mechanisms that represent the undesirable side effects of oxygen free radicals. First of all, these effects make the cell plasma membrane vulnerable and cause a series of intracellular functional disorders, as described by the membrane hypothesis of aging (MHA). The logical way for any antiaging intervention therefore should be to increase the available number of loosely bound electrons inside the plasma membrane that are easily accessible for OH• free radical scavenging. The present review summarizes the available knowledge regarding the theory of the use of membrane-related antiaging pharmaca, like centrophenoxine (CPH), tested in both animal experiments and human clinical trials. A modified, developed version of CPH coded as BCE-001 is also reported.



Today, one of the most widely accepted ideas regarding the biological aging process is the free radical theory of aging (FRTA) proposed and first tried mainly by Harman,1-8 and later followed by numerous authors. The basic concept of FRTA is that oxygen free radicals are harmful by-products of aerobic life and as such, are to be considered the main causal factors of aging and numerous diseases.

Although this idea has been widely accepted and implicated in a series of biological phenomena, a deeper analysis has revealed various contradictions, unexplained problems, and paradoxical situations. During the last decade, the present author has formulated the contradictory items of the FRTA,9-17 and, at the 8th IABG Congress held at Kyongju (South Korea), outlined a new, comprehensive interpretation of the possible biological role of oxygen free radicals in the living state, cell differentiation, and aging.18 It should be emphasized, however, that although this new concept implicitly contradicts the central dogma of the FRTA just mentioned, it does not obviate the possibility of damaging side effects of these radicals at specific places of the cell structure. The main difference between the FRTA and this new concept is that, according to the latter, the constant flux of oxygen free radicals is an implicit attribute of life, that is, the new concept offers a much wider basis for interpreting the free radical functions.

According to this new concept,18 the situation in living beings can be compared mutatis mutandis to that of electronic devices: in the latter, the supply current is an absolute prerequisite of their function, whereas the very same current may cause breakdowns in some components of the system through undesirable heating, crystal melting, or short-circuiting effects, to name a few. It means that a longer functional "life span" cannot be achieved for electronic devices by eliminating the electric current, but through better circuit design aimed at improving their ability to support the local, undesirable side effects of the current itself. This analogy means that for the living systems the continuous flux of oxygen free radicals always must be maintained during life, and we can only fight against the undesirable side effects of those radicals. In other words, the FRTA can remain valid with the following-modifications:


Theoretically, keeping in mind that totally blocking the oxyradical formation has a lethal effect, it is incorrect to propose, in general, eliminating any free radicals as an antiaging strategy.

Recognizing how important the production of oxygen free radicals is for the living state, one has to identify the free radical events that are actually involved in the age-dependent deterioration of brain functions at the cellular level.

Pharmacological interventions against aging have to be aimed at reducing only the really destructive radical effects, which may be possible only through the application of site-specific radical scavengers with well-defined and explored mechanisms of action.

The present review summarizes the available knowledge regarding the effects of a nootropic drug, centrophenoxine (CPH), as one that fulfills the listed criteria, the effects of which may be usefully interpreted in the light of this new approach.

The theoretical basis of this approach is the membrane hypothesis of aging (MHA).9-11,13,15,17,19-21 The MHA attributes a leading role in differentiation and aging processes to the plasma membrane, in which inevitable, continuous alterations occur during life. The alterations are due in part to free-radical-induced molecular damage, and also to the "residual heat" formed during each depolarization of the resting potential. These membrane alterations dictate the accumulation of dry mass (i.e., a decrease in the intracellular water content) in the intracellular space, which is a necessary process for the development and maturation, but becomes a rate-limiting factor above a certain physical density of the cell colloids. This statement is supported by the fact that the in situ enzyme activities in the cells are all strongly dependent on the density of their microenvironment. MHA is valid mainly for the postmitotic cells, such as neurons and muscle cells, and appears particularly evident as a single cycle in the erythrocytes where de novo protein synthesis does not take place. Recent developments in molecular genetics have strongly supported MHA, showing that the great majority of the products of oncogenes or antioncogenes (e.g., gas, ras, kit, fgr, yes, yet, fsv, ros, met, erb, neu, trk, fms oncogenes, senescence-associated gene, schwannomin gene, prohibitin gene, mortalin gene, p53 and p21 gene, statin gene, gerontogenes, etc.) have a more or less close plasma membrane localization.17,21 These facts confirm the central role of the plasma membrane in the realization of mitotic regulation, cell differentiation, and senescence. Using this approach, one can expect a deeper understanding of the function of the intracellular physicochemical parameters in the cell functions, their governing role in the aging process, and the possibilities of an eventual intervention to prolong the useful life span in both animal and human trials.

Early Empirical Data on the Effects of CPH
CPH is an ester of p-chlorophenoxyacetic acid (PCPA) and dimethylaminoethanol (DMAE).22,23 We have reviewed the relevant early literature that considers its in vitro and in vivo effects.12 It is important to note that this drug, originally classified as "neuroenergeticum," is today one of the most frequently used types of nootropica in various countries.12 Nevertheless, in spite of a large number of experimental and clinical studies, the mechanism of CPH's effect on the age-dependent decline of mental performance mostly has been misinterpreted.12

In human therapy, a number of beneficial effects of CPH have been observed in cases like cerebral atrophy, brain injury, postapoplectic disorders, chronic alcoholism, and barbiturate intoxications.24-27

It has also been observed that prolonged administration of CPH to old animals that are in good health reduced significantly the accumulation of lipofuscin in the brain cells28 and myocardium (see Ref. 12). Furthermore, the average life span of these CPH-treated animals increased significantly, and the learning ability of the old mice that had received treatment improved as compared to their age-matched controls.29-32 On the basis of these results, CPH was considered to be a potential antiaging drug.12

Ideas About the Mechanism of Action
As regards CPH's mechanism of action, it was suggested that the DMAE moiety of CPH enters the choline synthesis cycle (and consequently improves the brain's acetylcholine supply).33,34 However, this explanation has been contradicted by others.34-36 It must be clear that an increase in the supply of choline when a fraction of DMAE from CPH is transformed into choline (which has been shown to take place in the liver; see Ref. 37) cannot be the only explanation for the effect of this drug, since in this case a choline-rich diet alone should have the same effect as CPH has, which is not the case.35,36 Further data on this problem also have been discussed.37

Important information has been revealed by intravenous administration of equimolar doses of 14C-labeled DMAE or CPH in Japan.38 After this intervention, much higher levels of DMAE were encountered in the brain after CPH treatment than with DMAE alone since, as was the case with earlier assumptions, the esterified form of DMAE with PCPA penetrates the blood-brain barrier much better.38 CPH was hydrolyzed on both sides of the barrier in its two component parts in vivo. However, the DMAE moiety becomes phosphorylated in the brain, yielding phosphoryl-DMAE, which was in turn converted to phosphatidyl-DMAE, apparently the end-metabolite of DMAE in the brain.38 Phosphatidyl-DMAE is incorporated in nerve cell membranes, and persists in this form for a relatively long time in place of choline.38 This means that DMAE forms a special class of phospholipids in the brain cell membranes. PCPA moiety is excreted in the urine rather quickly, apparently without any metabolic change.38 It should be noted that although some amount of DMAE administered either alone or in the form of CPH was found in acid-soluble and lipid cholines in the brain,38 there is evidence that the trimethylation of DMAE does not occur in the brain, but only in the liver.38 Therefore, the presence of DMAE in the nerve cell membrane phospholipids had to be considered the starting point of any approach to the mechanism of CPH action.

Evidence of the OH• Radical Scavenger Properties of CPH
Special experiments have been carried out in order to reveal whether the effects of DMAE on brain functions can be interpreted in terms of a local oxyradical protecting effect on the cell membrane components.

Protein Cross-Linking Model
The basic concept of this type of experiment is that the OH• free radicals generated in a Fenton reagent,39 or by a Co-gamma irradiation,40 react with the proteins (e.g., bovine serum albumin = BSA), altering their molecular structure. One can detect either a decrease in the protein's water solubility (originally 100% for BSA), and an increase in its average molecular weight, as a result of cross-linking,39 or an increase in its carbonyl content as a result of protein oxidation.40 It has been shown in such studies that DMAE efficiently inhibits both the polymerization of BSA induced by the OH• free radicals generated in the Fenton reaction and the radiation-induced oxidation of them.39,40 These results clearly show that DMAE is an efficient OH• radical scavenger.

Electron Spin Resonance Spectroscopy in Spin-trapping Experiments
The electron spin resonance (ESR) spectroscopy technique applies specially designed compounds (spin traps), the reactions of which with various types of free radicals are well known. The spin trapping experiments demonstrated that the CPH molecule and both of its components display a strong affinity toward the OH• radicals.41 The reaction-rate constant of DMAE can be estimated to be about 109 M-1s-1 with OH• free radicals.41 Since most of the bioorganic compounds react with OH• radicals at a rate of 107-109 M-1s-1,42 DMAE really may represent an essential protection for numerous cell-membrane components against OH• free radical attacks.

Although these experiments also revealed an OH• radical scavenger capacity of the PCPA moiety of the CPH molecule, PCPA cannot be responsible for the nootropic effects of CPH, since no binding of this compound is known in the brain. It cannot be excluded, however, that this moiety of CPH may have some physiologically meaningful effect in the blood or in some other tissues (e.g., kidney or liver) during its excretion.

It should also be noted that although CPH and both its components display some affinity toward the superoxide radicals, their rate constant is only on the order of magnitude of 102 M-1s-1, that is, there is no reason to assume that either the components or the CPH molecule itself would represent any efficient protection in vivo against superoxide-radical-induced damage.43

The Molecular Design of BCE-001
As has been pointed out in a recent review,44 the reactivity of DMAE with OH• free radicals is most probably due to the trivalent nature of the nitrogen atom in the dimethlyamino group of DMAE. This nitrogen atom still has two loosely bound electrons that are able to take part in radical reactions more easily than the other, more strongly bound electrons of the molecule. In order to test this idea, we designed several new molecules during the early 1980s, starting from the concept that a doubling of the loosely bound electrons per molecule may increase the rate constant of the OH• radical scavenging activity of the moiety. Before describing this new molecule, it might be useful to repeat here some conceptual statements from the previous review.44 It is due to the extremely short lifetime of the OH• free radicals that protection of the neuronal membrane components against OH• radical damage only can be imagined if the following criteria are fulfilled.


The scavenger molecule should have a reaction rate with OH• radicals comparable to that of the target molecule to be protected.

The scavenger should get sufficiently close to the target and remain there as a component part for a sufficiently long time.

The scavenger must not exert any deleterious side effect (toxicity) for the organism in general or in the immediate vicinity of the target molecule.

These criteria suggest that it is most probably a hopeless effort to test various scavengers without having any particular knowledge about their molecular biology, binding sites, and so forth. It should be stressed that so far most of the studies on the dietary antioxidants unfortunately have been performed without having such special information. For example, Weber and Miquel45 reviewed the available data on the effects of a large number of radical scavenger compounds. Although some antioxidant supplements were indeed capable of extending the life span of experimental animals, the observed effects were not at all consistent when compared with the same drug in various species.45

Considering the preceding principles and the results obtained with CPH, we designed a new drug, coded BCE-001. It is basically similar to CPH, the difference being that the PCPA moiety is esterified with 1,3-bis(dimethylamino)-2-propanol (BIDIP) instead of DMAE. Details have been described before,44 so we will not repeat them here. Nevertheless, it should be pointed out that BIDIP contains two dimethylamino groups, that is, twice as much loosely bound electrons are available in this moiety for the neutralization of OH• radicals. The consequence of this molecular structure was a 1.9-fold increase in the molecule's reaction-rate constant with the OH• free radicals, as measured in spin-trapping experiments, which is quite close to the theoretically expected 2-fold increase. As has been described before,44 this property of the molecule is biologically meaningful, since it proved to be an efficient nootropic agent of low toxicity in vivo, which can be administered orally or even parenterally.44 To the best of our knowledge, this was the first case of designing a new molecule on the basis of the available knowledge that proved to be efficient in antiaging experiments. This fact is of great importance, apart from the eventual success of this molecule in human antiaging prevention. The development of this molecule for human use is currently under way.

Animal Experiments
Obviously, neither the presence of DMAE in the brain nerve-cell membranes38 nor the in vitro OH• radical scavenging ability of this compound41 proves directly that it also acts as an OH• radical scavenger in vivo. However, numerous experimental results, listed only briefly below, demonstrate indirectly that the presence of DMAE or BIDIP in the cell membrane is of physiological significance, which can be attributed to their local OH• radical scavenger properties.

Effects on Lipid Fluidity and Protein Molecular-Weight Distribution in Synaptosomal Membranes
Aging causes an increase in microviscosity of the membrane lipids in the synaptosomal membranes. This parameter can be measured by means of fluorescence polarization techniques after diphenyl-hexatriene (DPH) labeling of brain cortical synaptosomal membranes.46 After treatment of old rats with CPH for 60 days,46 or with BCE-001 for 20 days (unpublished results), the membrane microviscosity decreased again significantly (to about the same extent after both treatments), as shown by the DPH method.

Spin labeling ESR techniques47 confirmed the validity of the results obtained by DPH labeling for both drugs (unpublished results). These results show indirectly that BIDIP also reaches the brain synaptosomal membranes, although direct investigations with radiolabeled components have not been carried out. Synaptosomal membranes were well protected by CPH pretreatment against the toxic effect of acute Fe2+ overload in the cerebrospinal fluid of young rats in vivo;48 therefore, similar effects also can be expected from BCE-001.

The molecular-weight distribution of the proteins is considerably shifted toward the higher values in the synaptosomes of the rat brain cortex during aging. This is a clear sign of an increased cross-linking of the membrane proteins. Treatment for 60 days with CPH49 or for 20 days with BCE-001 (unpublished results) reversed this tendency to a significant extent in old rats.

All these results indicate that BCE-001 treatment improves the previously mentioned physicochemical properties of the neuronal membranes about 2-3 times faster than did CPH.

Effects on the Lateral Mobility of Proteins and Lipids in the Cell Membrane
The lateral mobility of membrane proteins and lipids was measured using fluorescence recovery after the photobleaching (FRAP) technique.50 The lateral diffusion constant of hepatocyte membrane proteins (Dp) displays a characteristic negative linear-age correlation in Fischer 34450,51 and Wistar52 rats, in C57BL black mice,53 in wild mouse strains of considerably different longevity (Peromyscus leucopus, Mus musculus),54 BN/Bi rats,55 as well as SAM mice.56 The same finding has been described for the ConA-receptor proteins in the skeletal muscle cells of mice57 and in the large brain cortical cells of rats.58 Although it is almost by an order of magnitude faster than Dp, membrane lipid lateral mobility (Dl), showed very similar age-dependence in hepatocyte mernbranes.59

The striking fact is that although the absolute values and the rates of age-dependent decays of protein and lipid mobilities in the cell membranes of various tissues are different, they are inversely proportional to the life span of the given strain. In the case of the wild mouse strains mentioned earlier, there exists a 2.6-fold difference in longevity in favor of P. leucopus, and the age-related decline of Dp is about 2.5-times slower in the longer-living species.54

FRAP experiments on two-year-old Fischer 344 rats pretreated per os through a gastric tube with aqueous solutions of 80 mg/kg CPH or BCE-001 for five weeks revealed a significantly higher value of Dp than in the controls. BCE-001 produced a quantitatively larger increase of the protein diffusion constant using an identical dosage and time of treatment, than did CPH.60 Another important observation was that the well-known, almost linear body weight loss of the Fischer 344 male rats above the age of two years was slightly inhibited by CPH from the end of the third week of treatment, whereas in the BCE-001-treated group this loss of body weight was almost entirely stopped after one week of treatment.60 This result indicates that the observed increase in Dp under the effect of CPH or BCE-001 is not only an improvement in the cellular parameter, but it is also meaningful from a general physiological point of view. Inhibition of the body weight loss in these animals is very convincing evidence for the overall improvement of the status of the animals, and is in agreement with the observed life-prolonging effect of BCE-001. It is also noteworthy that caloric restriction experiments on mice also increased the Dp values to an extent that might correspond with the life-prolonging effect of this intervention.61

Effects on the Passive Potassium Permeability of the Nerve-cell Membranes
As explained by the MHA, the age-dependent decline of the passive potassium permeability in the nerve cells is a key issue in brain aging. CPH treatment for 60 days (80-100 mg/kg) in old rats reincreased the passive potassium permeability of the neuronal-cell membrane, that is, it decreased the intracellular potassium content and rehydrated the cytoplasm of brain neurons significantly.62,63 BCE-001 had the same effect, though a lower dose (60 mg/kg) and a shorter period (3-4 weeks) of treatment were sufficient to reach the same level as these improvements in rats (unpublished observations).

These findings indicate that CPH and BCE-001 may be useful in the prevention or therapy of age-dependent brain disorders.

Effects on the Rates of Total and mRNA Synthesis in the Brain Cortex
The rate of synthesis of total, as well as mRNA, was measured using radioisotope methods in vivo in rats. An age-dependent decrease in the rates of total and mRNA synthesis was observed in the brain cortex of rats between 1 and 2 years of age (to 40-50% of the young-adult value).64 The significance of this phenomenon in the age-dependent decrease in protein turnover rates has been clearly shown by MHA to be the main reason for the loss of physiological abilities of all cells and organs.

In vivo treatments with both CPH and BCE-001 reversed this tendency. CPH treatment for 60 days reincreased these rates to 80-90%,65 whereas BCE-001 resulted in similar increases after 40 days, and values up to 113% were obtained when the drug was applied for 60 days (unpublished results). Therefore, BCE-001 is not only a better OH• radical scavenger than CPH, but it is able to stimulate more efficiently the in vivo rates of brain RNA-synthesis. This fact may be of great significance in the prevention or therapy of human brain disorders like dementias, where decreased RNA and protein synthesis is an obvious reason for the dysfunctions.

Survival Experiments
It has been observed by various authors that CPH treatment prolonged the medium life span of laboratory animals, especially if the treatment started at relatively young ages. It also improved the learning ability of several animal species (see Refs. 63 and 66). In some cases an increase in the medium life span of up to 30% was described in mice, but only if the CPH treatment started at the age of 6 months.

The effect of BCE-001 on the medium life span was studied in one experiment when female CFY rats were treated intraperitoneally (i.p.) from the age of 18 months. The untreated controls displayed a medium life span of 23.6 months, which is a quite usual value for this strain. The BCE-001 treatment increased the medium life span of these rats to 29 months (unpublished results). Per os treatments with BCE-001 increased the medium life span by almost 10 months (unpublished results).

Some Further Animal Experiments
BCE-001 was tested in comparison with CPH in further behavioral and other animal models on the basis of commissions from BIOGAL Pharmaceutical Works, Ltd. (Debrecen, Hungary) in various laboratories in Japan and Hungary. Although the results have not been published, we can mention here briefly the following results: doses of 60-100 mg/kg of BCE-001 administered i.p. for 7-30 days in rats improved the brain functions. It displayed an effect on the neurotransmitters, in particular increasing the 5-HT content in the septum, and improved memory functions through a novel mechanism of action. It was particularly active in the hippocampus and modified its dopaminergic system. It increased the glucose utilization in the brain regions involved in memory and awakening, such as the frontal cortex, nucleus basalis, nucleus lateralis thalami, hippocampus, and reticular formation. BCE-001 exerted a protective action against experimentally induced hypoxia, manifesting itself in a longer survival period. It also inhibited the formation of strokes in spontaneously hypertensive rats. It therefore can be considered to be a cerebrovascular protective agent acting without any prolonged modification of the systemic circulation. Various tests on memory consolidation and retrieval demonstrated that BCE-001 has beneficial effects that are comparable to that of CPH; therefore, the possibility of developing a useful nootropic drug for human use seems to be realistic. It is important to stress here that in comparison to CPH, BCE-001 displayed a more advantageous effect in each of the listed experiments.

Human Experiments with CPH
Several persons around the age of 40, including the author of the present review, started to take CPH (500 mg/day) in 1976, and maintained this experimental treatment until now. Due to the relatively low number of these subjects, this cannot be considered a scientific experiment; nevertheless, all the participants agree that they maintained better physical and mental performance than the untreated persons in their family of similar age. Apart from this observation, it is important to note that the treated persons had no side effects, even after 25 years.

In order to create a basis of comparison for future human applications of BCE-001, specially designed human experiments were performed, and their results are summarized follows. In a double-blind, randomized human clinical trial, CPH treatment for 8 weeks improved the psychometric and behavioral performance in about 50% of patients with a medium level dementia (according to the DSM III, Cat. 1, or ICD No. 299): the placebo group displayed improvement in only 27% of cases.66 A considerable rehydration of the intracellular mass was observed in the verum group at the expense of the extracellular liquid. Meanwhile, body weight remained unchanged.67 These data are mentioned here to demonstrate that nootropica, like CPH (and most probably also like BCE-001), also behave in humans in the same predictable way as MHA. Similar human trials will be performed with BCE-001 as soon as the drug achieves human phase II of testing.


CONCLUSIONS AND PERSPECTIVES

The synthetic interpretation of the biological aging phenomena offered by the MHA represents an interdisciplinary approach for describing a cellular mechanism that offers a generally valid explanation for the effects of oxygen free radicals, and that offers a good chance for experimental testing. On the basis of the MHA, the design of a special drug that proves to be efficient could be realized, in good agreement with the theoretical predictions.

The assumption that only site-specific OH• free radical scavengers can be considered seriously as potential preventive antiaging drugs seems to be well supported by the experimental facts. Besides the eventual success or failure of the BCE-001 in future human trials, the most important theoretical message of the reviewed results is that proper improvement of the defense against OH• free radical attacks in the brain cell membrane is beneficial. Following this line, newly designed drugs, which may be helpful in achieving a real breakthrough in geriatric prevention and care, seem to be worth pursuing.

It should be emphasized that even a future life span-prolonging strategy should be based on the FRTA; nevertheless, we have to apply the new concepts outlined in this review. Due to the by now explored properties of the OH• radical reactions, only site-specific, nontoxic, and physicochemically feasible radical protection offer any hope of success. It should also be stressed that in highly evolved living systems, where the natural radical protection is a priori much more efficient than in rodents, it is highly probable that only multifactorial radical protection can be successful in improving the natural defence system.

#17 REGIMEN

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Posted 12 August 2005 - 10:49 PM

Capping Centro-
I'm going to try mixing it with Taurine today for encapsulation in single-0 size caps. I'll let you know how it goes.

#18 xanadu

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Posted 12 August 2005 - 11:15 PM

Capping it does not seem very challenging. Do up 50 caps and weigh them, figure about 115mg for the weight of each gel cap and you have the dose per cap.

rshack, that was a good article. I liked the part about how the author had been using it for 25 years with no observed side effects. It also seemed to make the rats live longer but it's hard to extrapolate that to humans.

#19 johnmk

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Posted 13 August 2005 - 07:22 PM

Is a full, stuffed cap going to give one a bit too much CPH?

#20 xanadu

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Posted 13 August 2005 - 07:43 PM

If you have no way of weighing them, figure about 600mg in a 00 cap. An 0 cap might be roughly 400mg. Invest in a cheap scale. Make up 50 caps full and weigh them. Weigh the empty caps first and subtract from the finished weight. Then, divide by 50. Even a postal scale will give you a fairly accurate figure.

#21 rshack

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Posted 13 August 2005 - 10:08 PM

I take it you are buying centrophenoxine bulk and not in capsultes. Could you please tell me the source? Thanks

#22 xanadu

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Posted 14 August 2005 - 05:29 PM

I got mine from the supplier list. I believe it was CNW. As I recall, I paid about $20 for 25gm. I haven't capped it up yet but plan to start taking it. I bought some caps and a few capMquicks. It takes about 15 minutes to do 50 caps.

Edited by xanadu, 15 August 2005 - 05:11 PM.


#23 REGIMEN

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Posted 15 August 2005 - 01:39 AM

johnmk

Is a full, stuffed cap going to give one a bit too much CPH?


A full cap of either the most widely used capsule (0 & 00) would certainly be too much Centro.
You'll need a filler to mix it with; I happen to have some extra Taurine like I mentioned for such a purpose.
Best to use something that is also best assimilated on an empty stomach.

#24 xanadu

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Posted 15 August 2005 - 05:17 PM

Is centro more dense than other noots? A packed 0 cap of most things is only about 400mg. I was going to make up some 0 caps but I have #1 caps also and a #1 cap m quick. Unpacked caps are even lighter but might vary in weight. I have some #3 caps but no cap m quick for them. I might be able to use my #1 machine with the #3 caps.

I thought centro was supposed to be taken with food? If not, you could cut it with gaba or inositol.

#25 johnmk

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Posted 15 August 2005 - 08:59 PM

Do you think there'd be a problem with CPH and creatine monohydate in the same pill?

#26 GhostBuster

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Posted 02 December 2011 - 05:45 PM

Bump.

What do you think about centrophenoxine, experiences? I am considering giving it a shot . It should reduce lipofuscin in the brain and in the skin in relatively short time. Also increases choline in the brain and extends lifespan by 30 % (in mice) etc.

#27 pycnogenol

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Posted 03 December 2011 - 03:04 PM

Bump.

What do you think about centrophenoxine, experiences? I am considering giving it a shot . It should reduce lipofuscin in the brain and in the skin in relatively short time. Also increases choline in the brain and extends lifespan by 30 % (in mice) etc.


I'm also thinking about taking centrophenoxine. I'm in the researching phase at the moment.

http://www.hubmed.or...oxine&sort=date

#28 Geoffrey

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Posted 03 December 2011 - 03:23 PM

I take it as my main choline source, because I find it a little easier to get the right dose than I do with CDP-Choline or Alpha-GPC. It tastes sour at first, but after you’ve washed it down, there is a lingering sweet taste which is not unpleasant. I find it’s best not to take any other choline source with it – whenever I’ve taken a small amount of CDP while dosed up on Centro, I get a severe stiff neck.

As for the effects, they are similar to other nootropics, although I have to say I have only rarely taken it on its own. On the occasions I have, it seems to increase greatly the effect of any residual oxiracetam or aniracetam that might be in my system. In general, it feels to me that very small doses of the -racetams have quite a big effect when supplementing with centrophenoxine. But I have always "suffered" from disorientating effects and sometimes extreme fatigue (especially with piracetam) if I take the normal recommended dose of the -racetam, so my experience with centrophenoxine may not be typical at all.

I should add that I tend to take only about an eighth of a teaspoon of centro, maybe twice or three times a day when I’m microdosing on aniracetam or oxiracetam (a tenth of the “recommended” doses). For me, this combo has very noticeable effects of sensory brightening and subjective effects of faster memory recall in general.

#29 AgeVivo

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Posted 03 December 2011 - 09:00 PM

If so, then centro might be an anti aging compound as well as a brain stimulant. I haven't seen any claims that it extends life.

I've discussed with people from Russia who told me centrophenoxine had been tested in rats and extended their lifespan, the results came during the perestroika so they were not published.

=> it would be nice to test centrophenoxine again, in correct conditions.

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#30 GhostBuster

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Posted 04 December 2011 - 03:30 PM

Article on centrophenoxine:

Centrophenoxine - the neuroenergizer

http://www.worldheal...neuroenergizer/

Studies on centrophenoxine:

http://www.lef.org/p...enoxineabs.html

Pubmed studies

- Centrophenoxine increased activity of Catalase, Superoxide Dismutase, Glutathione reductase, as well as an increase in the reduced, oxidized, and total glutathione content

- Lipid peroxidation was also reported to be significantly decreased in aged animals after Centrophenoxine supplementation for 6 weeks. The use of an extraneous antioxidant substance may prove beneficial in combating the conditions of oxidative stress in ageing brain.

PMID: 16137852

- CPH significantly attenuated rotenone-induced depletion in DA, GSH and increase in LPO levels. In addition, the drug prevented the increase in nitric oxide (NO) and citrulline levels and also enhanced the activity of catalase and superoxide dismutase (SOD).

19375462

- posttreatment with centrophenoxine significantly elevated the superoxide and catalase activities in different regions

20021037

- Centrophenoxine also reduced lipofuscin deposits (studied both biochemically and histochemically) thus indicating that the drug inhibited lipofuscin accumulation by elevating the activity of the antioxidant enzymes.

6416880

Increase in SOD etc. activity seems to be a factor that reduces lipofuscin and cross linking. I wonder if that is the common denominator of different antioxidants?




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