2626 replies to this topic

[summertimex]

I am an undergraduate student working on a degree in Mathematics. My challenge this summer is Linear Algebra and Matrix Theory condensed into a mini-semester 6-week crash course.

A few days before the start of the semester I began taking (in the morning):

• 12.5 mg Forskolin (125mg capsules at 10%)
• 300mg Solaray Artichoke extract
• A dopaminergic compound (<5mg methylphenidate, 500mg l-tyrosine, ginko, et al)

I also take Lamotrigine daily to manage Bipolar Disorder and other nonpsychoactive supplements for general health.

I've been using this stack 5 days a week, and I'm about to enter my fourth week of class. Right now I have an A average in the course and I scored 100 on a test for the first time in a few years.
Although I'm skilled with mathematics, in the past my grades have suffered greatly because of test anxiety and ADD-like problems related to Bipolar Disorder. The anxiety of a test situation causes a stress reaction that significantly hinders my ability to think or remember and then I end up distracted by my own thoughts, at times I have been unable to complete tests because of this problem.
It's clear to me that this stack is making a difference, because scoring 100 on a test was not possible for me in the recent past.

I feel like CILTEP has allowed me to absorb information more quickly and store it in long-term memory more readily than I would have otherwise. Like abelard lindsay reported, I can sit down and soak up information in long sessions without becoming fatigued. When I get up in the morning, all the information I learned the day before is easy to access, as if I had just learned it.

I'll report back in a few weeks.

Oxiracetam stacked well with niacinamide/b12 and alpha-gpc for economics. The interaction between oxi and ciltep seems fine to me, but i havent tested it in a course.

[abelard lindsay]

So after taking the Hesperidin stack on the second day I noticed that the effects were very strong. Perhaps there's a cumulative effect over two days? As an experiment, I took a day and a half off the stack and had one of my lazy weekend days that were common before I started this stack. Very relaxing and pleasant but I'm too used to being able to sit down and read a programming book for 6 hours straight whenever I want to with good information retention so it was a little disconcerting that I wasn't able to do that without the stack.

Anyway, I think Hesperidin (Swanson Brand) is a net positive addition, but only one pill at a time (500mg). Two is a little much, especially with two artichoke.

On a side note: Hesperidin turns into hesperetin when digested. I can't find anything particularly negative about it on pubmed. In fact there are quite a few health benefits to taking it:

http://www.ncbi.nlm....pubmed/22484922

Biosci Biotechnol Biochem. 2012;76(4):640-5. Epub 2012 Apr 7.
Anti-aging effects of hesperidin on Saccharomyces cerevisiae via inhibition of reactive oxygen species and UTH1 gene expression.
Sun K, Xiang L, Ishihara S, Matsuura A, Sakagami Y, Qi J.
Source

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Abstract

This study used a replicative lifespan assay of K6001 yeast to screen anti-aging food factors in commercial flavonoids. Hesperidin derived from the Citrus genus extended the lifespan of yeast at doses of 5 and 10 µM as compared with the control group (p<0.01, p<0.01). Reactive oxygen species (ROS), real-time PCR (RT-PCR), and lifespan assays of uth1 and skn7 mutants with the K6001 background were used to study the anti-aging mechanisms in yeast. The results indicate that hesperidin significantly inhibits the ROS of yeast, and UTH1 gene expression, and that SKN7 gene are involved in hesperidin-mediated lifespan extension. Further, increases in the Sir2 homolog, SIRT1 activity, and SOD gene expression were confirmed at doses of 5 (p<0.01) and 10 µM (p<0.05). This suggests that Sir2, UTH1 genes, and ROS inhibition after administration of hesperidin have important roles in the anti-aging effects of yeast. However, the aglycon hesperetin did not exhibit anti-aging effects in yeast.

What is it with all these PDE4 inhibitors extending lifespan? Remember the study about Resveratrol getting its life extending benefit from PDE4 inhibition? I think I posted this earlier... I'll just quote it briefly:

http://www.ncbi.nlm....pubmed/22304913

Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases.
....

Inhibiting PDE4 with rolipram reproduces all of the metabolic benefits of resveratrol, including prevention of diet-induced obesity and an increase in mitochondrial function, physical stamina, and glucose tolerance in mice. Therefore, administration of PDE4 inhibitors may also protect against and ameliorate the symptoms of metabolic diseases associated with aging.

Edited by abelard lindsay, 25 June 2012 - 05:41 AM.

[abelard lindsay]

So some people are private messaging me and asking what the heck is the Hesperetin for again? Briefly, my theory is that since it's a more selective PDE4 inhibitor than artichoke, but is weaker, combining the two would result in a stronger CILTEP effect with fewer side effects.

There are two ways that I've gone wrong with this stack. First, triggering what are known as PDE4H or "high-affinity rolipram binding sites". For instance, Genistein does this (http://www.ncbi.nlm....pubmed/20599919). This causes gastrointestinal disturbances. The other problems arise from strongly inhibiting non-PDE4 subtypes. This is caused by using a herbal PDE4 inhibitor with non-selective inhibition. For instance, PDE3 inhibition has undesirable side effects. See (http://en.wikipedia..../PDE3_inhibitor). PDE2 may have some use as a memory enhancer (http://www.ncbi.nlm....pubmed/16968949). PDE1 inhibition is considered a possible drug target for treating neuro-degenertive diseases(http://www.ncbi.nlm....pubmed/15798894). PDE5 is what Viagra and Cialis inhibit and you all know what those do.    So basically PDE3 inhibition is the one to avoid and I haven't really heavily looked into the non PDE4 ones, so I would not bother with specifically targeting them.

So these two issues cause the PDE4 inhibitor effect to be limited by the side effects of inhibition of other PDEs, mainly 3, and from the PDE4H effects (gastrointestinal disturbances).

Artichoke (Luteolin) IC50 values:
http://www.ncbi.nlm....pubmed/19853596

PDE1-5 activities, with K(i) values of 15.0, 6.4, 13.9, 11.1, and 9.5

So it's inhibiting PDE2, PDE5 and PDE4, most selectively. However PDE3 is getting inhibited and PDE4H is also getting activated:

The therapeutic (PDE4(H)/PDE4(L)) ratios of luteolin and Ro 20-1724 were calculated to be 0.6, and 0.004 ... In conclusion, because of the low therapeutic (PDE4(H)/PDE4(L)) ratio of luteolin, the gastrointestinal adverse effects such as nausea, vomiting and gastric hypersecretion should be carefully monitored, whenever luteolin is used for treating allergies, asthma or chronic obstructive pulmonary disease.

Well I haven't experienced any nausea or vomiting or stomach problems at the two pills or less of artichoke, so I guess I'm not taking enough to encounter these problems at these dosages. Going past taking two pills is not advised.

The bright side of this is that PDE4 inhibition is still low at the dosages I'm taking and there's plenty of room for improvement. In order to get to higher PDE4 inhibition a way needs to be found around the side effects by choosing a more selective PDE inhibitor that has no action at PDE3 and is more selective for PDE4 and doesn't trigger PDE4H receptors.

Enter Hesperetin

http://www.ncbi.nlm....pubmed/22454667

Hesperetin was revealed to have a therapeutic (PDE4(H)/PDE4(L)) ratio of >11
...
The respective EC₅₀ (PDE4_H) values of rolipram, Ro 20-1724, and hesperetin for displacing [³H]-rolipram binding were 7.5 ± 3.4 (n = 4) nM, 45.6 ± 9.7 (n = 4) nM, and >300μM.

So since high values mean less effectiveness, Hesperetin was several orders of magnitude less likely to trigger PDE4H than the highly targeted synthetic PDE4 inhibitors.

On to PDE inhibition
http://www.ncbi.nlm....pubmed/22074248

HDME did not inhibit PDE2 or PDE5 activities (IC₅₀ value > 100 μM), but it concentration-dependently inhibited PDE1, PDE3, and PDE4 activities with respective IC₅₀ values of 22.1 ± 6.4 (n = 4), 24.6 ± 3.5 (n = 4), and 3.0 ± 0.9 μM (n = 4)
The IC₅₀ value of HDME (Lipid Soluble Hesperetin) for PDE4 inhibition was significantly less than those for PDE1 and PDE3 inhibition.

So the lipid soluble version was roughly 7x more selective on PDE4 than PDE3 or PDE1!

The non lipid soluble version also was more selective
http://www.ncbi.nlm....pubmed/15476679

Hesperetin and prunetin exhibited more-selective inhibition of PDE4 with IC(50) values of around 30 and 60 microM,

So the PDE4 inhibition of Hesperetin that is not chemically tweaked to be fat soluble is about 1/10th the tweaked version. If the same holds true for PDE3 and PDE1 then their inhibition is very small.

So anyway, makes me wonder if I should just replace Artichoke with Hesperetin.

The problem is that Hesperetin has a weak ic50 value for PDE4 inhibition. Thus, I would theorize that if I stacked artichoke underneath it, it will further push up PDE4 inhibition such that it gets a little higher with minimal side effects from PDE3 inhibition and PDE4H binding. I could take a Hesperetin only stack to minimize any possible issues. Maybe 2 Hesperetin and 1 Artichoke?

You're probably wondering how is good ol' Quercetin stacking up?
http://www.sciencedi...006295204004770

The same was true for quercetin, but we rather consider that it more-selectively inhibited PDE3 and PDE4 (IC₅₀ of <10 μM).

So since I don't want strong PDE3 inhibition, I'll probably avoid Quercetin.

I'll report back later this week if the Hesperetin stack tweak works. So far so good.


TL;DR

Hesperetin has less side effects as a PDE4 inhibitor than Artichoke but is weaker. Adding a Hesperetin to the stack seems to help improve the effect without causing negative effects. Might consider halving my artichoke dose and replacing it with Hesperetin.

Edited by abelard lindsay, 25 June 2012 - 08:24 AM.

[Raza]

How long does the hesperedin last, compared to artichoke and quercetin?

[gizmobrain]

Would there be any reason to go with Hesperedin over Diosmin?

[abelard lindsay]

How long does the hesperedin last, compared to artichoke and quercetin?

Probably 12 to 18 hours. It does seem to leak into the next day though.

Would there be any reason to go with Hesperedin over Diosmin?

There's nothing in the literature about Diosmin being a PDE4 inhibitor. That doesn't mean it isn't of course.


Hesperetin Update:

Wow.. Nice effect! I took it at about 4pm last night and slept pretty badly. Next time I'll dose first thing in the morning. It was very nice before I fell asleep and helped me be very sociable. Oddly, I got up at 8:30 and had a productive day despite sleeping badly. I came up with some pretty good fixes to some complex problems at work. People were impressed. Things were a little "swimmy" but not uncomfortably so. It takes some getting used to I guess. I really enjoyed reading computer books today. I even started to crave it a bit. The experience was different than artichoke, stronger in some ways, and very anxiolytic. It does take some getting used to and seems to effect stacks taken the next day.

[gizmobrain]

I understood Diosmin to be the lipid soluble version of hesperetin. Is this false?

[Raza]

Probably 12 to 18 hours. It does seem to leak into the next day though.

Thanks!

I really enjoyed reading computer books today. I even started to crave it a bit. The experience was different than artichoke, stronger in some ways, and very anxiolytic. It does take some getting used to and seems to effect stacks taken the next day.

I'd be careful with common habits on this stack. Extra LTP may well enhance one of the mechanisms for habit/addiction, the one with the sensitized neural pathways for oft-repeated and rewarding activities. Learning is more dopaminergically rewarding than it used to be on this stuff.

I understood Diosmin to be the lipid soluble version of hesperetin. Is this false?

I thought so too and looked it up, but can't find confirmation. The name of the substance in AL's article is different from any name I can find Diosmin by.

Edited by Raza, 26 June 2012 - 07:42 AM.

[gizmobrain]

Ah, I see where my confusion lied. Glad I asked

Found how to cook it up:

Hesperetin-7,3'-O-dimethylether (HDME) is synthesized according to the method described by Fumiss et al [31]. In the beginning, 100 mg of hesperetin are dissolved in the appropriate volume of dioxane and added the reacted diazomethane (yellow liquid) thereinto, and then this mixture is posited in the hood at the room temperature for about 18 hours. The reacted mixture is separated by silica gel column (where the mobile phase thereof is ethyl acetate:benzene:n-hexane=1:2:3) and fractionated by 15 ml per fraction. The fractions are analyzed by TLC for obtaining the distribution of HDME, and specific fractions containing HDME are collected and dried out to obtain raw HDME. The raw HDME is dissolved in a minimum volume of dichlomethane for purification. Then, large amounts of methanol are added in the dissolved raw HDME and took it in the ice bath for crystallization. After decreasing the pressure and filtering the mixture, white and crystallized HDME is obtained (where the yield rate and mp thereof are 32.7% and 132.5-134.4quadrature respectively).

Read more: http://www.faqs.org/...8#ixzz1yt5zPcI9

Hey, I just spotted this:

Planta Med. 1995 Jun;61(3):213-6.
Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects.

Viola H, Wasowski C, Levi de Stein M, Wolfman C, Silveira R, Dajas F, Medina JH, Paladini AC.

Source

Instituto de Biología Celular, Facultad de Medicina, Buenos Aires, Argentina.

Abstract

The dried flower heads of Matricaria recutita L. (Asteraceae) are used in folk medicine to prepare a spasmolytic and sedative tea. Our fractionation of the aqueous extract of this plant led to the detection of several fractions with significant affinity for the central benzodiazepine receptor and to the isolation and identification of 5,7,4'-trihydroxyflavone (apigenin) in one of them. Apigenin competitively inhibited the binding of flunitrazepam with a Ki of 4 microM and had no effect on muscarinic receptors, alpha 1-adrenoceptors, and on the binding of muscimol to GABAA receptors. Apigenin had a clear anxiolytic activity in mice in the elevated plusmaze without evidencing sedation or muscle relaxant effects at doses similar to those used for classical benzodiazepines and no anticonvulsant action was detected. However, a 10-fold increase in dosage produced a mild sedative effect since a 26% reduction in ambulatory locomotor activity and a 35% decrement in hole-board parameters were evident. The results reported in this paper demonstrate that apigenin is a ligand for the central benzodiazepine receptors exerting anxiolytic and slight sedative effects but not being anticonvulsant or myorelaxant.

I believe my high Nature's Herbs Artichoke extract might be quite high in Apigenin. This might account for the "swimmy" feeling when taking too much.

Edited by zrbarnes, 26 June 2012 - 08:52 AM.

[abelard lindsay]

Just to be clear, when I say the stack feels "swimmy" I mean it feels similar to how taking a lot of lion's mane feels. It's an anxiolytic feeling. I always thought this was caused by NGF activity.

Edited by abelard lindsay, 26 June 2012 - 04:40 PM.

[Rior]

So my question is...where does one acquire Hesperetin? I've been looking around and can't seem to find any legitimate supplement vendors with it, only overseas vendors.

Edit: Ah hah. I just realized I've been searching Hesperetin, vs hesperedin. Big difference in results there.

On this note though, what dosage have you been taking Abelard Lindsay?

Edited by Izat04, 26 June 2012 - 05:06 PM.

[gizmobrain]

Just to be clear, when I say the stack feels "swimmy" I mean it feels similar to how taking a lot of lion's mane feels. It's an anxiolytic feeling. I always thought this was caused by NGF activity.

I can't relate to the Lion's Mane, since the brand I trialed once seemed to do absolutely nothing.

The "swimmy" I've referred to throughout this thread is definitely anxiolytic. Beyond that, there is a minor change in visual perception, and if I close my eyes the world... swims. Its not spinning; it doesn't mess with my balance; it doesn't make me nauseous, but it's there. I'm pretty sure what I'm describing is related to benzo/gaba activity.

It happens if I take too much of the Nature's Herb Artichoke, or if I take Solaray Rosemary Extract (which both have benzo/gaba related compounds), but does not happen with Quercetin.

Something I've wanted to try but haven't yet, is to combine Rosemary/Artichoke with Gingko to see if this blocks the "swimmy"-ness.

Of course, it's pretty hard to know if the "swimmy" I'm talking about is the same as the "swimmy" you are talking about. It's a pretty subjective subject

Edited by zrbarnes, 26 June 2012 - 06:08 PM.

[summertimex]

Is the hesperdin extract from orange peels? If it is it might contain nobiletin also.

http://www.mendeley....hosphorylation/


If there is competitive ligand binding the Luteolin would cancel out the PDE4 effect, but that isnt mentioned. If you do adderall and caffeine they dont cancel each other out exactly.

Edited by gen6k, 26 June 2012 - 06:29 PM.

[summertimex]

calcium/calmodulin dependent - PDE1
cGMP stimulated - PDE 2
CGMP inhibited - PDE 3
cAMP specfic - PDE 4
cGMP specific- PDE 5

It might be better to keep the Luteolin to stabalize the PDE3 buildup. Since the IC50 value for PDE 2 is low.

Edited by gen6k, 26 June 2012 - 06:32 PM.

[abelard lindsay]

So my question is...where does one acquire Hesperetin? I've been looking around and can't seem to find any legitimate supplement vendors with it, only overseas vendors.

Edit: Ah hah. I just realized I've been searching Hesperetin, vs hesperedin. Big difference in results there.

On this note though, what dosage have you been taking Abelard Lindsay?

Hesperetin and hesperedin are roughly the same. One turns into the other when digested. Today I took 2 Swanson brand Hesperedin pills (about 1 gram). I think this stuff works.

I found this interesting study today:

http://www.ncbi.nlm....pubmed/22451307

J Alzheimers Dis. 2012 Jan 1;30(3):665-73.

Pyruvate Prevents the Inhibition of the Long-term Potentiation Induced by Amyloid-β through Protein Phosphatase 2A Inactivation.

Wang X, Takata T, Bai X, Ou F, Yokono K, Sakurai T.

Source

Department of Gerontology and Geriatrics, The First Affiliated Hospital of China Medical University, Shenyang, China.

Abstract

Amyloid-β (Aβ) oligomers are derived from proteolytic cleavage of amyloid-β protein precursor and can impair memory and hippocampal long-term potentiation (LTP) in vivo and in vitro. They are recognized as the primary neurotoxic agents in Alzheimer's disease. Pyruvate has a protective effect against Aβ-induced neuronal cell death in hippocampal slice cultures. However, whether pyruvate also has a protective effect against the inhibition of neuronal plasticity induced by Aβ remains to be elucidated. This study examined the effect of pyruvate on the Aβ-induced inhibition of LTP in the rat hippocampus. We found that pyruvate prevented the Aβ-induced inhibition of LTP as strong as fostriecin, a specific protein phosphatase 2A (PP2A) inhibitor. Pyruvate prevented the Aβ block of Ca2+/calmodulin dependent protein kinase 2 (CaMK2) autophosphorylation and the Aβ-induced PP2A activation. Pyruvate, but not lactate, decreased reactive oxygen species levels in CA1 slices exposed to Aβ. We propose that pyruvate could prevent the Aβ-induced inhibition of LTP by the re-autophosphorylation of CaMK2 through PP2A inactivation. The reduction of reactive oxygen species production is considered to be the upstream mechanism of this observed pyruvate protection.

On a philosophical note, I've started to notice how boring my life is. I can recall my daily grind with so much detail that I start to marvel at how each day is so similar to all the others.

Edited by abelard lindsay, 27 June 2012 - 06:22 AM.

[Junk Master]

Abelard Lindsay, would you mind posting a recap of your stack? Hesperedin and forskolin?

[X_Danny_X]

Should I use Hesperetin if I take Forskholin and Quercetin? Quercetin also inhibits COMT?

I am also taking the following stack below.


Selegiline for dopamine increase
ALCAR for other nootropic benefits
Fish Oil for other nootropic benefits
Spirulina for healthy benefits and Uridine (yeah not proven how effective is Uridine from Spirulina, but that is another issue)
CRAZE Preworkout thing for whatever benefits it has. It has Vitamin C and also Caffeine.
Ashwaghanda for more brain cognitive enhancement and whatever else it gives (such as better sleep)
Melatonin for sleep and helping to increase growth hormone production. I feel like superman when waking up.

Quercetin (with Branelain) for PDE4 and PDE5 inhibition. Reading this thread showed me that Quercetin also inhibits COMT. I was thinking of taking Cat's Claw but if Quercetin works in being COMT inhibitor, I wont buy Cats Claw.
This guy I take to also enhance executive function since that is what happens when you inhibit COMT.
Forskolin for reasons already explained in this thread and for working out.
Caffeine The CRAZE supplement thing has caffeine but might need a kick though doubtful if I am taking Quercetin.

Edited by X_Danny_X, 28 June 2012 - 02:08 AM.

[abelard lindsay]

Abelard Lindsay, would you mind posting a recap of your stack? Hesperedin and forskolin?

I'm permuting my stack around a bit right now with all the components I've listed previously. I'm looking for the right balance. I'm still trying to figure Hesperetin and Pyruvate out. I also take about 700mg of piracetam and some CDP choline daily. The default stack is still 2 Now Artichoke pills, 3.85mg Forskolin and 2 Now L-Phenylalanine + Caffeine throughout the day.

Should I use Hesperetin if I take Forskholin and Quercetin? Quercetin also inhibits COMT?

I haven't had much experience with Hesperetin + Quercetin. I imagine it would be pretty strong. I searched for COMT and Hesperetin together and didn't find anything.

Edited by abelard lindsay, 28 June 2012 - 06:13 AM.

[X_Danny_X]

not Hesperetin but Quercetin when it comes to inhibiting COMT. I would like to know if Quercetin inhibits COMT. If so then I wont need to buy Cats Claw.

I just took my first dose of my stack. Both Quercetin and Forksholin are in powder form. I have no idea how much I am taking each time since there is no measuring instrument for me.

Edited by X_Danny_X, 28 June 2012 - 10:51 AM.

[abelard lindsay]

not Hesperetin but Quercetin when it comes to inhibiting COMT. I would like to know if Quercetin inhibits COMT. If so then I wont need to buy Cats Claw.

I just took my first dose of my stack. Both Quercetin and Forksholin are in powder form. I have no idea how much I am taking each time since there is no measuring instrument for me.

Just for the record, I find it's good to be careful about the dosages when taking this stack and not measuring dosages is a bad idea. Too much can be over-stimulating and annoying. I find GABA is good to counteract the effects of taking too much.

Edited by abelard lindsay, 28 June 2012 - 11:47 AM.

[X_Danny_X]

not Hesperetin but Quercetin when it comes to inhibiting COMT. I would like to know if Quercetin inhibits COMT. If so then I wont need to buy Cats Claw.

I just took my first dose of my stack. Both Quercetin and Forksholin are in powder form. I have no idea how much I am taking each time since there is no measuring instrument for me.

Just for the record, I find it's good to be careful about the dosages when taking this stack and not measuring dosages is a bad idea. Too much can be over-stimulating and annoying. I find GABA is good to counteract the effects of taking too much.

Is is necessary to take Leutonin if I am taking Forksholin and Quercetin?


I use GABA to help me sleep at night. Seems these nootropics are giving me sleeping problems since they help charge up your brain. So far combining GABA and Ashwaghanda and Melatonin has help me sleep interrupted for 6 hours. I know that is not alot but I have issues with sleeping for a few months now. Sleeping for 4 hours, cant sleep then in the late morning, my body passing out again to sleep for a couple of hours.

Finally I am sleeping at least for now 6 hours STRAIGHT. Hope to increase it to 8 hours.

Edited by X_Danny_X, 28 June 2012 - 12:21 PM.

[abelard lindsay]

Is is necessary to take Leutonin if I am taking Forksholin and Quercetin?

I think you meant Luteolin? You do not need to take both. Either one by itself will work. L-Phenylalanine or another dopamine pre-cursor is needed for the best effect though.

Here's a study that says Quercetin is a suspected COMT/MAO Inhibitor
http://www.ncbi.nlm....pubmed/12711835

Pharmacology. 2003 Jun;68(2):81-8.
Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition.
Singh A, Naidu PS, Kulkarni SK.
Source

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Abstract

L-Dopa plus carbidopa treatment remains the first-line therapy in Parkinson's disease. The use of catechol-O-methyltransferase (COMT) and/or monoamine oxidase (MAO) inhibitors as an adjunct to L-dopa therapy has yielded varying degrees of success. Quercetin, a flavonoid present in many plants, is reported to inhibit COMT and MAO activities, the key enzymes involved in the metabolism of dopamine. In the present study we have studied the effect of quercetin on the L-dopa plus carbidopa combination against perphenazine and reserpine-induced catalepsy in rats. Neuroleptic-induced catalepsy is a widely accepted animal model for testing the drugs used in parkinsonism. Catalepsy in rats was induced by administration of perphenazine (5 mg/kg i.p.) or reserpine (2.5 mg/kg i.p.) + alpha-methyl-P-tyrosine (200 mg/kg i.p.). Catalepsy in animals was assessed by using the bar test. The quercetin dose (25-100 mg/kg, p.o.) dependently reversed perphenazine- as well as reserpine-induced catalepsy. When quercetin was combined with a subthreshold dose of L-dopa plus carbidopa, the anticatatonic effect was potentiated. Pretreatment with a central COMT inhibitor, 3,5-dinitrocatechol (OR-486) (10 mg/kg p.o.), or a MAO-B inhibitor, selegiline (5 mg/kg i.p.), also potentiated the actions of threshold dose of quercetin against perphenazine- or reserpine-induced catalepsy. On the other hand adenosine (100 mg/kg i.p.), which is known to decrease the release of catecholamines through an action on presynaptic A(1) receptors, partly reversed the protective effect of quercetin against perphenazine-induced catalepsy. Quercetin through its COMT and MAO enzyme-inhibiting properties might potentiate the anticatatonic effect of L-dopa plus carbidopa treatment. The results of the present study strongly suggest that quercetin could serve as an effective adjunct to L-dopa therapy in Parkinson's disease.

Copyright 2003 S. Karger AG, Basel

PMID:
12711835
[PubMed - indexed for MEDLINE]

Edited by abelard lindsay, 28 June 2012 - 12:48 PM.

[X_Danny_X]

Is is necessary to take Leutonin if I am taking Forksholin and Quercetin?

I think you meant Luteolin? You do not need to take both. Either one by itself will work. L-Phenylalanine or another dopamine pre-cursor is needed for the best effect though.

Here's a study that says Quercetin is a suspected COMT/MAO Inhibitor
http://www.ncbi.nlm....pubmed/12711835

Pharmacology. 2003 Jun;68(2):81-8.
Quercetin potentiates L-Dopa reversal of drug-induced catalepsy in rats: possible COMT/MAO inhibition.
Singh A, Naidu PS, Kulkarni SK.
Source

Pharmacology Division, University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India.
Abstract

L-Dopa plus carbidopa treatment remains the first-line therapy in Parkinson's disease. The use of catechol-O-methyltransferase (COMT) and/or monoamine oxidase (MAO) inhibitors as an adjunct to L-dopa therapy has yielded varying degrees of success. Quercetin, a flavonoid present in many plants, is reported to inhibit COMT and MAO activities, the key enzymes involved in the metabolism of dopamine. In the present study we have studied the effect of quercetin on the L-dopa plus carbidopa combination against perphenazine and reserpine-induced catalepsy in rats. Neuroleptic-induced catalepsy is a widely accepted animal model for testing the drugs used in parkinsonism. Catalepsy in rats was induced by administration of perphenazine (5 mg/kg i.p.) or reserpine (2.5 mg/kg i.p.) + alpha-methyl-P-tyrosine (200 mg/kg i.p.). Catalepsy in animals was assessed by using the bar test. The quercetin dose (25-100 mg/kg, p.o.) dependently reversed perphenazine- as well as reserpine-induced catalepsy. When quercetin was combined with a subthreshold dose of L-dopa plus carbidopa, the anticatatonic effect was potentiated. Pretreatment with a central COMT inhibitor, 3,5-dinitrocatechol (OR-486) (10 mg/kg p.o.), or a MAO-B inhibitor, selegiline (5 mg/kg i.p.), also potentiated the actions of threshold dose of quercetin against perphenazine- or reserpine-induced catalepsy. On the other hand adenosine (100 mg/kg i.p.), which is known to decrease the release of catecholamines through an action on presynaptic A(1) receptors, partly reversed the protective effect of quercetin against perphenazine-induced catalepsy. Quercetin through its COMT and MAO enzyme-inhibiting properties might potentiate the anticatatonic effect of L-dopa plus carbidopa treatment. The results of the present study strongly suggest that quercetin could serve as an effective adjunct to L-dopa therapy in Parkinson's disease.

Copyright 2003 S. Karger AG, Basel

PMID:
12711835
[PubMed - indexed for MEDLINE]

Yeah that is what I meant. Good thing, I guess I will put it back in the box for now and use it when I run out of Quercetin and Forksholin.

I am taking Selegiline right now for Dopamine increase. I didn't realize that Quercetin is also a MAO enzyme inhibitor. Selegiline is a MAO-B inhibitor, what is Quercetin? I am a little worried now that I am over doing it with MAO inhibition?

Edited by X_Danny_X, 28 June 2012 - 01:24 PM.

[oryx]

I used this stack (3-6 mg forskolin+2-3 artichoke+ritalin er) for close to two weeks, with great success the first 5 or so days, followed by progressively feeling more and more tired, earlier and earlier in the day, until I finally decided to stop. On my final day on the combo, I felt so lethargic I couldn't bring myself to get anything done. I'm disappointed since initially this had just the effect for my ADD inattentive symptoms I've needed.
I'm still a little out of it and weirdly over-tired. Perhaps this is due to the acetylcholine desensitization? Hoping I get back to normal soon. Just wanted to put in my 2 cents.

[summertimex]

I used this stack (3-6 mg forskolin+2-3 artichoke+ritalin er) for close to two weeks, with great success the first 5 or so days, followed by progressively feeling more and more tired, earlier and earlier in the day, until I finally decided to stop. On my final day on the combo, I felt so lethargic I couldn't bring myself to get anything done. I'm disappointed since initially this had just the effect for my ADD inattentive symptoms I've needed.
I'm still a little out of it and weirdly over-tired. Perhaps this is due to the acetylcholine desensitization? Hoping I get back to normal soon. Just wanted to put in my 2 cents.

In early may I started a hardcore racetam stack pira, ani, oxi, pram daily then later may added artichoke+forksolin. I'm starting to slow down now and need to redose racetams 3 times a day with protein (neurotransmitters). Some of which calm me down more (trytophan).
My brain is still changing from both types of LTP, ciltep and ampakine. But especially the pram has made my mood and experiantiality more flat. Which is a good thing for now.

You probably need to supplement more dopamine precursors, and try different ADD methods.


This study explains the high potency ampakine BDNF trigger is desensitized, but not if its alternated. Another way is to use less.

Chronic elevation of brain-derived neurotrophic factor by ampakines.

* Lauterborn JC,
* Truong GS,
* Baudry M,
* Bi X,
* Lynch G,
* Gall CM.

Department of Anatomy and Neurobiology, Gillespie Neuroscience Research Facility, University of California, Irvine, CA 92697-4292, UA. jclauter@uci.edu

The ampakine CX614 positively modulates alpha-amino-3-hydroxy-5methyl-4-isoxazolepropionic acid (AMPA) receptor-gated currents and increases brain-derived neurotrophic factor (BDNF) expression. In rat hippocampal slice cultures, CX614 rapidly increases BDNF gene expression but with time, mRNA levels fall despite the continued presence of active drug. The present study examined this apparent refractory period and the possibility that spaced ampakine treatments could sustain elevated BDNF protein levels. In cultured hippocampal slices, CX614, a second ampakine CX546, and the cholinergic agonist carbachol each increased BDNF mRNA levels with acute (3-h) treatment. After 4-day pretreatment with CX614, fresh ampakine (CX614 or CX546) did not induce BDNF mRNA, whereas carbachol did. Western blots confirmed that after an extended period of ampakine treatment, AMPA receptor protein levels are indeed reduced, suggesting that with longer treatments receptor down-regulation mediates ampakine insensitivity. Finally, using a "24-h on/24-h off" CX614 treatment protocol, the ampakine refractory state was circumvented, BDNF mRNA was induced with each ampakine application, and elevated BDNF protein levels were maintained through 5 days in vitro. These results suggest that spaced ampakine treatments can be used to sustain elevated neurotrophin levels and to test the utility of this manipulation for neuroprotection by endogenous neurotrophins.

PMID: 12893840 [PubMed - indexed for MEDLINE]

Edited by gen6k, 28 June 2012 - 09:18 PM.

[FrankMH]

Would a Dopamine agonist such as Piribedil, serve to fulfil the Dopamine role suggested? I'm being allured by the potential for an increase in Working Memory capacity; and if it could work in conjunction with a stack like this, could it be winner?

[gizmobrain]

I used this stack (3-6 mg forskolin+2-3 artichoke+ritalin er) for close to two weeks, with great success the first 5 or so days, followed by progressively feeling more and more tired, earlier and earlier in the day, until I finally decided to stop. On my final day on the combo, I felt so lethargic I couldn't bring myself to get anything done. I'm disappointed since initially this had just the effect for my ADD inattentive symptoms I've needed.
I'm still a little out of it and weirdly over-tired. Perhaps this is due to the acetylcholine desensitization? Hoping I get back to normal soon. Just wanted to put in my 2 cents.

For those who are getting sleepy: Does Galatamine knock out the sleepiness? I've noticed that 8mg of Galantamine will take the punch out of the sleepiness, which seems to confirm that it has something to do with acetylcholine, but I'd need someone else to test this to make sure its not just my own reaction to Galantamine.

If so, we need to come up with a way to quickly re-sensitize the choline receptors, either while sleeping, or on the weekends.

Edited by zrbarnes, 28 June 2012 - 09:47 PM.

[magta39]

I used this stack (3-6 mg forskolin+2-3 artichoke+ritalin er) for close to two weeks, with great success the first 5 or so days, followed by progressively feeling more and more tired, earlier and earlier in the day, until I finally decided to stop. On my final day on the combo, I felt so lethargic I couldn't bring myself to get anything done. I'm disappointed since initially this had just the effect for my ADD inattentive symptoms I've needed.
I'm still a little out of it and weirdly over-tired. Perhaps this is due to the acetylcholine desensitization? Hoping I get back to normal soon. Just wanted to put in my 2 cents.

For those who are getting sleepy: Does Galatamine knock out the sleepiness? I've noticed that 8mg of Galantamine will take the punch out of the sleepiness, which seems to confirm that it has something to do with acetylcholine, but I'd need someone else to test this to make sure its not just my own reaction to Galantamine.

If so, we need to come up with a way to quickly re-sensitize the choline receptors, either while sleeping, or on the weekends.

Yes.. the same happened to me...I stopped the forskolin and took galantamine 8mgs for 3 days to resensitize my receptors.

[gizmobrain]

Thanks for the confirmation.

Interestingly enough, some people use Galantamine as a sleep aid...

[oryx]

Unfortunately, I don't know how to access galantamine. I took lecithin yesterday, but I had a weird reaction in the form of a severe panic attack to some combination of the supplements I'd taken along with it. Whether the lecithin was partially responsible, I have no idea, but don't feel like trying my luck either. Hopefully it won't take too long for my brain to go back to normal on its own? I think I'm done experimenting with my brain for the time being.