What do you guys think of low dose Alpha GPC as a nootropic? Something like 300mg at breakfast with other noops…
BBB and others, what do you make of this?
“Vinpocetine – Ditch It, Not good for many reasons, cognitively…”
BBB and others, what do you make of this? it’s from another forum
"I have come to the conclusion that vinpocetine should be eradicated from our supplement stashes. This is due in light of evidence brought about by “dopamine” who is now posting more frequently on our boards.
This is taken from M & M, a thread started by dopamine.
QUOTE
Vinpocetine (ethyl apovincaminate) is a synthetic derivative of the alkaloid vincamine (from the periwinkle plant vinca minor) and has cerebral blood-flow enhancing (1) and voltage sensitive Na+ channel inhibiting properties (2), leading to it’s use as a drug in Hungary, Germany and Russia in the treatment of cerebrovascular dementia and Alzheimer’s disease (3). Vinpocetine has also become popular supplement in the United States, and is often marketed to otherwise healthy individuals for improvement of memory and self-treatment of age-associated memory decline. Though the specific mechanism of action of vinpocetine has not been fully elucidated, effects on the dopaminergic system have been scarcely investigated.
Trejo F et al, 2001 reported on the “Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings” and found that vinpocetine increases DOPAC release, while simultaneously decreasing vesicular dopamine storage in a similar fashion as reserpine - an indole alkaloid with antipsychotic and antihypertensive properties with some structural similarities to vinpocetine (4). The authors report in the results section that “vinpocetine at increasing concentrations progressively decreases internal DA and increases DOPAC release” and “markedly inhibits DAT-mediated release of endogenous DA.” (5)
The effects of vinpocetine on DA and DOPAC levels are not believed to be related to the well-demonstrated inhibitory effects on voltage sensitive Na+ channels, as “vinpocetine increases DOPAC release independently of the state of presynaptic VSSC.” A possible MAO-A enhancing mechanism is ruled out “as vinpocetine fails to modify the inhibition of DOPAC formation caused by clorgyline” - a potent inhibitor of MAO-A, “indicating that a reserpine-like mechanism is involved in the vinpocetine-induced increase in DOPAC formation.” (6)
If vinpocetine does indeed act in a “reserpine-like” fashion in striatal dopaminergic neurons, one could legitimately raise concern over the use of vinpocetine in otherwise healthy individuals for “cognitive enhancement,” as side effects may manifest consistent with reserpine-like side effects, including depression and cognitive dysfunction (7, 8). Because resperine inhibits VMAT-2, the protein primarily responsible for the transportation of monoamines from the cytosol to synaptic vesicles, the amount of dopamine, norepinephrine and serotonin stored in neurons may be substantially decreased pre-synaptically by vinpocetine, leading to a downregulation of monoaminergic tone.
In other words, while vinpocetine may be neuroprotective under some experimental and clinical conditions, it may also interfere with monoamine storage, and affect the way in which the brain responds to drugs acting through dopaminergic, adrenergic, or serotonergic pathways (e.g. amphetamine, modafinil, methylphenidate, cocaine, SSRIs, bupropion, etc). Serious consideration should be given before taking vinpocetine, as it is a highly active pharmacological agent that interacts and interferes with a wide array of brain systems and functions.
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Szilágyi G, Nagy Z, Balkay L, Boros I, Emri M, Lehel S, Márián T, Molnár T, Szakáll S, Trón L, Bereczki D, Csiba L, Fekete I, Kerényi L, Galuska L, Varga J, Bönöczk P, Vas A, Gulyás B. “Effects of vinpocetine on the redistribution of cerebral blood flow and glucose metabolism in chronic ischemic stroke patients: a PET study.” Journal of Neurological Sciences 2005 Mar 15;229-230:275-84. Epub 2005 Jan 8. PMID: 15760651. [abstract]
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Sitges M, Galván E, Nekrassov V. “Vinpocetine blockade of sodium channels inhibits the rise in sodium and calcium induced by 4-aminopyridine in synaptosomes.” Neurochemistry International 2005 Jun;46(7):533-40. PMID: 15843047. [abstract]
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“Vinpocetine. Monograph.” Alternative Medicine Review 2002 Jun;7(3):240-3, pp. 240. PMID: 12126465. [full text]
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Trejo F, Nekrassov V, Sitges M. “Characterization of vinpocetine effects on DA and DOPAC release in striatal isolated nerve endings.” Brain Research 2001 Aug 3;909(1-2):59-67. PMID: 11478921. [abstract]
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Ibid, pp. 61.
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Ibid, pp. 64.
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Huffman JC, Stern TA. “Neuropsychiatric consequences of cardiovascular medications.” Dialogues in Clinical Neuroscience 2007;9(1):29-45. PMID: 17506224. [abstract]
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Cai JX, Ma YY, Xu L, Hu XT. “Reserpine impairs spatial working memory performance in monkeys: reversal by the alpha 2-adrenergic agonist clonidine.” Brain Research 1993 Jun 18;614(1-2):191-6. [abstract]
Then I noticed through researching studies that vinpocetine has a negative impact on the NMDA receptors and the AMPA receptors. These are two very important receptor systems that substances claimed of being nootropics should elicit a positive affect on or no affect at all. Here are two studies which show vinpocetine have a negative affect on them, I THINK!
QUOTE
Effects of several cerebroprotective drugs on NMDA channel function: evaluation using Xenopus oocytes and [3H]MK-801 binding.
Kaneko S, Sugimura M, Inoue T, Satoh M.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
The effects of several cerebroprotective and nootropic drugs on the function of excitatory amino acid (EAA) receptor subtypes expressed in Xenopus oocytes after injection of rodent brain poly(A)+ mRNA were investigated. The oocyte response to N-methyl-D-aspartate (NMDA) in the presence of glycine (Gly) was inhibited dose-dependently by bifemelane, indeloxazine, vinpocetine and vincamine while no effect was observed by idebenone, Ca hopantenate, aniracetam or piracetam. Bifemelane, indeloxazine and vinpocetine suppressed the maximum response of NMDA and Gly without affecting their EC50 values. Unlike Mg2+, they did not affect the current-voltage relationship of the NMDA response below 0 mV. On the non-NMDA-type responses of the injected oocytes to kainate (KA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and quisqualate (QA), no significant effects were observed by these drugs at 100 microM. On the binding of 3H-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imi ne (MK-801) to brain membranes, the estimated IC50 values were 88 microM for bifemelane, 102 microM for indeloxazine, and 115 microM for vinpocetine. The dissociation rate of [3H]MK-801 was significantly slowed by Zn2+ and vinpocetine, but not affected by bifemelane or indeloxazine. The Kd value for [3H]MK-801 binding was increased by bifemelane and indeloxazine while Bmax was unchanged. These results suggest that the inhibition of NMDA channels by vinpocetine shows a similarity to the action of Zn2+ which closes the gate of the NMDA channel. In contrast, bifemelane and indeloxazine may affect the phencyclidine (PCP)-site in the open channels and inhibit NMDA function.
PMID: 1652446 [PubMed - indexed for MEDLINE]
AND THIS ONE FOR AMPA
QUOTE
Vinpocetine preferentially antagonizes quisqualate/AMPA receptor responses: evidence from release and ligand binding studies.
Kiss B, Cai NS, Erdö SL.
Pharmacological Research Centre, Gedeon Richter Ltd., Budapest, Hungary.
The effect of vinpocetine on excitatory amino acid receptors was examined in the rat brain by two different biochemical approaches. In release experiments with striatal slices, vinpocetine reduced the efflux of dopamine and acetylcholine evoked by glutamate, quisqualate and N-methyl-D-aspartate (NMDA), but not that evoked by kainate. In binding experiments with cortical membranes, vinpocetine reduced the binding of [3H]2-amino-3-3-hydroxy-s-methylisoxasole-4-yl-propionic acid ([3H]AMPA), a quisqualate partial agonist, in an incomplete manner, but failed to influence the binding of [3H]kainate and [3H]3-(2-carboxypyperazine-4-yl)-propyl-1-phosphonic acid ([3H]CPP), an NMDA agonist. These findings suggest that vinpocetine is a quisqualate/AMPA antagonist of some specificity and selectivity.
PMID: 1687679 [PubMed - indexed for MEDLINE]
What do you all think? Dopamine, what are your thoughts on the studies I brought up and vinpocetine as a whole for its use in healthy individuals?"
[quote]Wise Guy wrote:
What do you guys think of low dose Alpha GPC as a nootropic? Something like 300mg at breakfast with other noops…[/quote]
It’s pretty expensive stuff, I tried some a while ago, got a couple of caps off someone and didn’t notice too much. I’d stick with the dmae, found it way much cheaper and effective.
Kim et al. Curcumin stimulates proliferation of embryonic neuiral progenitor cells and neurogenesis in the adult hippocampus. J Biol Chem 283(21):14497-505 (2008)
They found that curcumin promotes hippocampal neurogenesis in adult mice; 500 nmol/kg body weight of curcumin was administered intraperitoneally which, the authors estimate, resulted in roughly 1â??2 µM concentration in the brain. The researchers identified the neurogenic effect as being mediated by an ERK and p38 MAPK mechanism.
The researchers conclude that: â??relatively low doses of curcumin can stimulate hippocampal neuroplasticity, a finding with important implications for preventative and therapeutic approaches for a range of neurological disorders that involve impaired neurogenesis, including depression, diabetes, and AD [Alzheimerâ??s disease].â?? Uncontrollable stress is another inhibitor of neurogenesis.
Can anyone point me in the right direction to buy some aniracetam? ive searched google and there are some crap prices. It seems really hard to find now a days! … My PMs don’t work.
Neuropharmacology. 2009 Sep;57(4):463-71. Epub 2009 Jun 21
Curcumin reverses impaired cognition and neuronal plasticity induced by chronic stress.
Xu Y, Lin D, Li S, Li G, Shyamala SG, Barish PA, Vernon MM, Pan J, Ogle WO.
J Crayton Pruitt Family Department of Biomedical Engineering and Evelyn F & William L Mcknight Brain Institute, University of Florida, Gainesville, FL 32611, USA.
Chronic stress occurs in everyday life and induces impaired spatial cognition, neuroendocrine and plasticity abnormalities. A potential therapeutic for these stress related disturbances is curcumin, derived from the curry spice turmeric. Previously we demonstrated that curcumin reversed the chronic stress-induced behavioral deficits in escape from an aversive stimulus, however the mechanism behind its beneficial effects on stress-induced learning defects and associated pathologies are unknown. This study investigated the effects of curcumin on restraint stress-induced spatial learning and memory dysfunction in a water maze task and on measures related neuroendocrine and plasticity changes. The results showed that memory deficits were reversed with curcumin in a dose dependent manner, as were stress-induced increases in serum corticosterone levels. These effects were similar to positive antidepressant imipramine. Additionally, curcumin prevented adverse changes in the dendritic morphology of CA3 pyramidal neurons in the hippocampus, as assessed by the changes in branch points and dendritic length. In primary hippocampal neurons it was shown that curcumin or imipramine protected hippocampal neurons against corticosterone-induced toxicity.
i have read most of this thread and theres alot of great info so thanks guys. i was wondering what you would recommend to me. i want some extra help with revision for when its exam time. with what ive read im considering
piracetam + vinpocetine. also do consider that i live in the uk so obtaining some of these products might be difficult.
thanks
[quote]ojaysmoke wrote:
i have read most of this thread and theres alot of great info so thanks guys. i was wondering what you would recommend to me. i want some extra help with revision for when its exam time. with what ive read im considering
piracetam + vinpocetine. also do consider that i live in the uk so obtaining some of these products might be difficult.
thanks[/quote]
I would also add a choline source too, I prefere dmae. Don’t tend to react well to actual choline and this works better and cheap too.
The vinpocetine and dmae should be pretty easy to get hold of in the uk, I live there too. Normally buy from the states though, it works out cheaper including overseas postage, if your not in any rush to get it that is.
The piracetam is difficult to get hold of over here, I got mine about a year ago and there was plenty of suppliers around in the uk, but there aren’t any I can find now, must be some new law against it.
You can buy it from the states though, the shipping will probably be more than the piracetam itself, but still only works out about £30 altogether including shipping for 500g which will last ages.
[quote]imagination wrote:
ojaysmoke wrote:
i have read most of this thread and theres alot of great info so thanks guys. i was wondering what you would recommend to me. i want some extra help with revision for when its exam time. with what ive read im considering
piracetam + vinpocetine. also do consider that i live in the uk so obtaining some of these products might be difficult.
thanks
I would also add a choline source too, I prefere dmae. Don’t tend to react well to actual choline and this works better and cheap too.
The vinpocetine and dmae should be pretty easy to get hold of in the uk, I live there too. Normally buy from the states though, it works out cheaper including overseas postage, if your not in any rush to get it that is.
The piracetam is difficult to get hold of over here, I got mine about a year ago and there was plenty of suppliers around in the uk, but there aren’t any I can find now, must be some new law against it.
You can buy it from the states though, the shipping will probably be more than the piracetam itself, but still only works out about �?�£30 altogether including shipping for 500g which will last ages.[/quote]
thanks for info mate. also what dosages would you recommend for each?
[quote]ojaysmoke wrote:
thanks for info mate. also what dosages would you recommend for each?[/quote]
The usual dose is 2400 to 4800 mg per day in three divided doses.,
I would also suggest Oxiracetam. Some folks seem to prefer Aniracetam over Pira or Pira over Ani but pretty much everyone agrees Oxi works pretty well.
Look into it.
[quote]holguint123 wrote:
Kind of going off of that, is someone pretty much screwed if they go on a carb cycling diet (~125 g of carbs before a workout, simple/complex + P/F meals the rest of the day) when it comes to boosting brain power with these nootropics? Due to the restriction of carbs.
Also, I’ve been very curious if it is possible to have someone reach ketosis on a CKD diet much faster by allowing them to try and use their brain a lot “harder” than normal, since the brain uses the body’s glucose stores for energy. Or I guess a better question would be, how much does brain activity affect how fast someone gets back into ketosis, and if brain activity can be boosted through nootropics to achieve this. Totally a thought out in left field…haha random I know.[/quote]
I’m curious about the low carb data for Nootropics too.
Also, I know it was discussed that ECA would raise cortisol and thus inhibit memory formation, but what about something like HOT-ROX Extreme that doesn’t rely so heavily on only the speed effect as a fat burner?
How much caffeine is in HOT-ROX anyway? I’ve found small amounts (green tea) to be very beneficial when working and have had no issues with memory when using them but if the caffeine is like 200mg or something I could see it being an issue.
Any ideas?
Okay, fine, how about this?
Does anyone know how much caffeine is in a single pill of HOT-ROX?
That’s really the key point for me.
Can anyone recommend “Advance Physician Formulas” for there nootropics?
Im going to take
Vinpocetine 10mg
DMAE 130 mg (from 350 mg DMAE bitartrate)
twice a day and see how it goes.
On the label of my piracetam, it saids that the first time should be an attack dose~ around 4-8gm, any thoughts on this?
How long does it take to “fill up” choline stores with DMAE? Is it something I have to take for several weeks at least before I notice any effect?
For a week now I have taken 30 mg Vinpo plus DMAE (600 mg) plus Aniracetam (930 mg) every day with food. Haven’t noticed a difference yet, but I remember a friend saying it took him about two weeks to notice something.
Should I add something like Huperzine A to act as the ACh-esterase? Could that possibly help me out?
Either way, I bet I have some reading to do.