2626 replies to this topic

[medievil]

Dopamine D2 receptor upregulation in rat neostriatum following in vivo infusion of forskolin

Abstract:
INTRACEREBROVENTRICULAR (i.c.v.) forskolin infusion for 5 days resulted in a concentration-dependent increase in rat striatal dopamine (DA) D2 receptors measured with [3Hjraclopride. In animals given 50 nmol/h forskolin, the highest concentration used, raclopride-mediated suppression of spontaneous locomotor activity was attenuated, and (±)-7-hydroxy-dipropyl-amino-tetralin HBr (7-OH-DPAT)-mediated inhibition of striatal DA synthesis, as estimated by the accumulation of DOPA following inhibition of cerebral decarboxylase, was enhanced. These data suggest that the DA D2 receptor increase comprises receptors localized both post- and presynaptically. The density of striatal DA D1 receptors was also changed with the forskolin treatment, in a concentration-dependent fashion, but in the opposite direction to DA D2 receptors. These findings suggest that striatal DA receptor sensitivity can be changed by manipulation at the second messenger level (e.g. independent of direct neurotransmitter-receptor interactions) in vivo.

[medievil]

More stuff

"J Neurochem. 1998 Jun;70(6):2446-58.
Metabotropic glutamate receptor agonists potentiate cyclic AMP formation induced by forskolin or beta-adrenergic receptor activation in cerebral cortical astrocytes in culture.
Balázs R, Miller S, Chun Y, O'Toole J, Cotman CW.
Source
Institute for Brain Aging and Dementia, University of California, Irvine 92697-4540, USA.
Abstract
The metabotropic glutamate receptor (mGluR) agonist 1-aminocyclopentane-1S,3R-dicarboxylic acid (ACPD) potentiated the accumulation of cyclic AMP induced by either beta-adrenergic receptor stimulation (isoproterenol) or direct activation of adenylyl cyclase (AC) with forskolin in rat cerebral cortical astrocytes grown in a defined medium. In contrast, ACPD inhibits the cyclic AMP response in astrocytes cultured in a serum-containing medium. Pharmacological characterization indicated that a group I mGluR, of which only mGluR5 is detectable in these cells, is involved in the potentiation of cyclic AMP accumulation. Potentiation was elicited by mGluR I agonists [e.g., (R,S)-3,5-dihydroxyphenylglycine (DHPG)], but not by mGluR II or III agonists; it was pertussis toxin resistant and abolished by procedures suppressing mGluR5 function (phorbol ester pretreatment or DHPG-induced receptor down-regulation). Nevertheless, it appears that products generated through the mGluR5 transduction pathway, such as elevated [Ca2+]i or activated protein kinase C (PKC), are not involved in the potentiation as it was not influenced by either the intracellular calcium chelator BAPTA-AM or the PKC inhibitor Ro 31-8220. An inhibitor of phospholipase C, U-73122, markedly attenuated mGluR5-activated phosphoinositide hydrolysis but did not significantly affect the DHPG potentiation of the cyclic AMP response. A mechanism is proposed in which the potentiating effect on AC could be mediated by free betagamma complex that is liberated after the agonist-bound mGluR5 interacts with its coupled G protein."

[gamesguru]

Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells.


Abstract

A newly synthesized isoquinolinesulfonamide, H-89 (N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinoline-sulfonamide), was shown to have a potent and selective inhibitory action against cyclic AMP-dependent protein kinase (protein kinase A), with an inhibition constant of 0.048 +/- 0.008 microM. H-89 exhibited weak inhibitory action against other kinases and Ki values of the compound for these kinases, including cGMP-dependent protein kinase (protein kinase G), Ca2+/phospholipid-dependent protein kinase (protein kinase C), casein kinase I and II, myosin light chain kinase, and Ca2+/calmodulin-dependent protein kinase II were 0.48 +/- 0.13, 31.7 +/- 15.9, 38.3 +/- 6.0, 136.7 +/- 17.0, 28.3 +/- 17.5, and 29.7 +/- 8.1 microM, respectively. Kinetic analysis indicated that H-89 inhibits protein kinase A, in competitive fashion against ATP. To examine the role of protein kinase A in neurite outgrowth of PC12 cells, H-89 was applied along with nerve growth factor (NGF), forskolin, or dibutyryl cAMP. Pretreatment with H-89 led to a dose-dependent inhibition of the forskolin-induced protein phosphorylation, with no decrease in intracellular cyclic AMP levels in PC12D cells, and the NGF-induced protein phosphorylation was not not inhibited. H-89 also significantly inhibited the forskolin-induced neurite outgrowth from PC12D cells. This inhibition also occurred when H-89 was added before the addition of dibutyryl cAMP. Pretreatment of PC12D cells with H-89 (30 microM) inhibited significantly cAMP-dependent histone IIb phosphorylation activity in cell lysates but did not affect other protein phosphorylation activity such as cGMP-dependent histone IIb phosphorylation activity, Ca2+/phospholipid-dependent histone IIIs phosphorylation activity, Ca2+/calmodulin-dependent myosin light chain phosphorylation activity, and alpha-casein phosphorylation activity. However, this protein kinase A inhibitor did not inhibit the NGF-induced neurite outgrowth from PC12D cells. Thus, the forskolin- and dibutyryl cAMP-induced neurite outgrowth is apparently mediated by protein kinase A while the NGF-induced neurite outgrowth is mediated by a protein kinase A-independent pathway.

Forskolin: a specific stimulator of adenylyl cyclase or a diterpene with multiple sites of action?

Abstract

Forskolin, a naturally occurring diterpene, directly stimulates adenylyl cyclase and has been used extensively to increase cAMP and to elicit cAMP-dependent physiological responses. More recently, forskolin has been shown to inhibit a number of membrane transport proteins and channel proteins through a mechanism that does not involve the production of cAMP. Many of these channel proteins are predicted to have similar topographies in the membrane bilayer and it is tempting to speculate that forskolin may be binding at structurally homologous sites. Kenneth Seamon and colleagues discuss the cAMP-independent effects of forskolin and the structural similarity between forskolin and other physiologically important substances such as hexoses and steroids with respect to potential forskolin binding sites.

Edited by dasheenster, 24 May 2012 - 01:02 AM.

[abelard lindsay]

Hmm let's see

So looks like there's reversal of tolerance to stimulants going on; wich likely means the potentation also occurs to the anxiolytic benefits.

"Molecular mechanisms underlying forskolin-mediated up-regulation of human dopamine D2L receptors.

3. The forskolin-mediated hD2L receptor rise is dependent on de novo protein synthesis, a rise in cAMP levels, PKA activation, and, at least partially, PTX-sensitive G proteins. 4. Long-term increases in intracellular cAMP levels may change the sensitivity of a DA receptor expressing cell to DA by increasing D2 receptor density through enhanced cAMP-dependent transcription."

So PKA + cAMP together upregulate hD2L. Since we are supercharging cAMP here there should be even more upregulation of these receptors.

Dopamine D2 receptor upregulation in rat neostriatum following in vivo infusion of forskolin

The density of striatal DA D1 receptors was also changed with the forskolin treatment, in a concentration-dependent fashion, but in the opposite direction to DA D2 receptors. These findings suggest that striatal DA receptor sensitivity can be changed by manipulation at the second messenger level (e.g. independent of direct neurotransmitter-receptor interactions) in vivo.

Reconfirmation of the above but odd that it would act in the opposite way with D1 receptors.

Metabotropic glutamate receptor agonists potentiate cyclic AMP formation induced by forskolin or beta-adrenergic receptor activation in cerebral cortical astrocytes in culture.

A mechanism is proposed in which the potentiating effect on AC could be mediated by free betagamma complex that is liberated after the agonist-bound mGluR5 interacts with its coupled G protein."

So basically they are unsure why this agonist helped Forskolin increase cAMP. They propose an interaction but don't test it.

Inhibition of forskolin-induced neurite outgrowth and protein phosphorylation by a newly synthesized selective inhibitor of cyclic AMP-dependent protein kinase, N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89), of PC12D pheochromocytoma cells.


However, this protein kinase A inhibitor did not inhibit the NGF-induced neurite outgrowth from PC12D cells. Thus, the forskolin- and dibutyryl cAMP-induced neurite outgrowth is apparently mediated by protein kinase A while the NGF-induced neurite outgrowth is mediated by a protein kinase A-independent pathway.

Ok so cAMP induced neurite outgrowth works via Protein Kinase A. NGF induced doesn't.

Forskolin: a specific stimulator of adenylyl cyclase or a diterpene with multiple sites of action?

Abstract

Forskolin, a naturally occurring diterpene, directly stimulates adenylyl cyclase and has been used extensively to increase cAMP and to elicit cAMP-dependent physiological responses. More recently, forskolin has been shown to inhibit a number of membrane transport proteins and channel proteins through a mechanism that does not involve the production of cAMP. Many of these channel proteins are predicted to have similar topographies in the membrane bilayer and it is tempting to speculate that forskolin may be binding at structurally homologous sites. Kenneth Seamon and colleagues discuss the cAMP-independent effects of forskolin and the structural similarity between forskolin and other physiologically important substances such as hexoses and steroids with respect to potential forskolin binding sites.

So Forskolin has some inhibition at several different sites. I guess you have to pay the $30 to read the full paper to figure out which ones.... Sigh...

Anyway. I have some idebenone kicking around. It's basically slightly tweaked coenzyme q10. I might try this stack with that. It's always been a mild predictable mood brightener for me. I never really liked galantamine. It always felt a bit harsh. I'll have to read the research carefully to find out if I want to even consider stacking it.

Edited by abelard lindsay, 24 May 2012 - 04:33 AM.

[medievil]

The interesting thing is that forskolin would likely counteract the known tolerance issues to tyrosine too.

[medievil]

I started taking 500mg of quercetin today; see wheter that makes a difference allready with a stimulant.

[gamesguru]

I hate to cause an interruption in the thread, but I am wondering if anyone can chime in about how the proposed CILTEP stack will function in those with disabilities, particularly ADHD, autism spectrum, bipolar spectrum, and/or depressive spectrum? Please, feel free to relate CILTEP to other mental dysfunctions if you feel confident, as I'm sure everyone would be very interested to know if this stack provides any relief or worsens any symptoms which are commonly associated with "mental disorders".

[medievil]

As my shizophrenia is pretty much gone except the negatives i can only report back on those; i use stimulants for those. Increasing cAMP should help shizophrenia. Also AVPD and ADHD are both like "mini versions" of shizophrenia limited to only one negative.

[owtsgmi]

I hate to cause an interruption in the thread, but I am wondering if anyone can chime in about how the proposed CILTEP stack will function in those with disabilities, particularly ADHD, autism spectrum, bipolar spectrum, and/or depressive spectrum? Please, feel free to relate CILTEP to other mental dysfunctions if you feel confident, as I'm sure everyone would be very interested to know if this stack provides any relief or worsens any symptoms which are commonly associated with "mental disorders".

It seems to blast away the final lingering vestiges of SA I was experiencing. Only 3 days in though so not much to go on. The main observation so far is if I take coq10 100 mg with CILTEP before bed I get bad insomnia. I had been taking the coq10 without issues before that. I also think my dose of quercetin at 1mg may be too high also. I'll skip the coq10 and halve the quercetin today and see what happens.

What is the recommended quercetin dose with 9 mg forskolin?

[medievil]

Do you take a stim with this stack? the effects on your sa are interesting and probably explained by D2 upregulation as D2 and D3 are implicated in social behavor and its them making stims effective for sa.

[gizmobrain]

The main observation so far is if I take coq10 100 mg with CILTEP before bed I get bad insomnia.

You definitely don't want to take CILTEP (or even forskolin by itself) anytime near bedtime. It increases all kinds of process that produce cellular energy, so insomnia is nearly a given.

[gizmobrain]

I hate to cause an interruption in the thread, but I am wondering if anyone can chime in about how the proposed CILTEP stack will function in those with disabilities, particularly ADHD, autism spectrum, bipolar spectrum, and/or depressive spectrum? Please, feel free to relate CILTEP to other mental dysfunctions if you feel confident, as I'm sure everyone would be very interested to know if this stack provides any relief or worsens any symptoms which are commonly associated with "mental disorders".

As I've said previously in this thread, I have some form of ADHD-PI, SCT, or something (the doctor's call it ADHD-PI, but I've never been hyperactive). I basically have no motivation, and a terrible working memory (the upside is that I never really get stressed, and I think outside the box more than my peers). I think I fit the bill of having "poor executive functioning".

Outside of amphetamines, other stimulants do nothing for mental focus or motivation (actually, nothing has ever worked except amphetamines, out of everything I've tried). However, adding CILTEP makes just about any stimulant help with motivation and focus, even just plain ol' caffeine. This has been a Godsend to me because my insurance is about to expire, and I have been looking for a way to drop the amphetamines for almost 2 years now.

I plan to stick with Forskolin and Quercetin (it helps with my allergies a lot), but I still need to settle on a stimulant that I feel comfortable with using long term. I plan to try Guarana, Kola Nut, Catuaba, and Green Tea extracts. Also, I want to see how much Sublingual UMP (uridine) helps.

I finally feel like I respond to stimulants similar to the way "normal" people do (or maybe even sensitive people). If I drink an energy drink + CILTEP, it actually makes me feel like I'm Adderall, without all the terrible side effects.

BTW: this stack doesn't seem to increase my Digit Span score or my Dual N-Back performance in a noticeable way. I seem to be more lucid in everyday life, and I remember things that I feel like I would normally forget, but I still need help with the short term memory aspect.

Edited by zrbarnes, 24 May 2012 - 06:12 PM.

[owtsgmi]

Do you take a stim with this stack? the effects on your sa are interesting and probably explained by D2 upregulation as D2 and D3 are implicated in social behavor and its them making stims effective for sa.

Nothing I would necessarily call a stimulant, except for half a cup of normal coffee. These other supps may act as dopaminergics in some manner:

Uridine 250mg
L-theanine 100mg
Ultra B12 dropper
CoQ10 100mg

I've progressed through about 10 dopaminergics, but once I started uridine I find no need for them. Also, I am cutting back on the CoQ10 at bedtime (and will probably switch to 25mg in the am) because of insomnia.

[owtsgmi]

The main observation so far is if I take coq10 100 mg with CILTEP before bed I get bad insomnia.

You definitely don't want to take CILTEP (or even forskolin by itself) anytime near bedtime. It increases all kinds of process that produce cellular energy, so insomnia is nearly a given.

I took CILTEP in the am yesterday and was feeling normally tired at bedtime. Then, I took 100mg CoQ10 at bedtime and couldn't sleep all night. Won't happen again.

[medievil]

Quercetin added to a stim feels completely simular to high doses of resveratrol added to a stim; there's extra clarity and a distinct cognitive enhancement (can be placebo but my thinking seems differend) probably what ppl in this thread were looking for.
The addition of forskolin will probably make it really significant.

[gizmobrain]

Quercetin added to a stim feels completely simular to high doses of resveratrol added to a stim; there's extra clarity and a distinct cognitive enhancement (can be placebo but my thinking seems differend) probably what ppl in this thread were looking for.
The addition of forskolin will probably make it really significant.

That's how I ended up in this thread originally, before I knew about the Forskolin aspect (which is what made a huge difference). I had been trying to use Resveratrol to inhibit PDE4. Unfortunately, even a small dose of Resveratrol causes significant problems with my bodies ability to repair my muscles.

[trip96]

You guys think that horny goat weed (icariins) could work as a PDE-4 inhibitor? I know it is supposed to act as a PDE-5 inhibitor. Sorry for the brevity of this post but I am on my iPad and in a hurry. I just have some laying around and was wondering if I could substitute the artichoke or quercetin with horny goat weed to get this stack flowing.

Thanks and let me know.

[medievil]

Do you notice this weird feeling of cognitive enhancement with res added to a stim? Its hard to describe but its a unique feeling. Res felt even more potent then quercetine so im guessing it should def be a perfect alternative to quercetin for this stack.

[trip96]

You guys think that horny goat weed (icariins) could work as a PDE-4 inhibitor? I know it is supposed to act as a PDE-5 inhibitor. Sorry for the brevity of this post but I am on my iPad and in a hurry. I just have some laying around and was wondering if I could substitute the artichoke or quercetin with horny goat weed to get this stack flowing.

Thanks and let me know.

[medievil]

Im thinking this stack is the first piece of the puzzle in finding a replacement for amphetamine for several disorders; but who knows; it looks promosing.

Also it may be placebo but while i didnt notice my stim doses got stronger; i seem to be able to get away with using a smaller dose; ill keep everyone updated.

Edited by medievil, 24 May 2012 - 06:45 PM.

[gizmobrain]

It's been studied for it's effects as a PDE-4 inhibitor:

Asian J Androl. 2003 Mar;5(1):15-8.
Effects of icariin on cGMP-specific PDE5 and cAMP-specific PDE4 activities.

Xin ZC, Kim EK, Lin CS, Liu WJ, Tian L, Yuan YM, Fu J.

Source

Department of Urology, the 1st Hospital, Peking University, 8 Xishiku Street, Xicheng District, Beijing 100034, China. xinzc@bjmu.edu.cn

Abstract

AIM:

To clarify the mechanism of the therapeutic action of icariin on erectile dysfunction (ED).
METHODS:

PDE5 was isolated from the human platelet and PDE4 from the rat liver tissue using the FPLC system (Pharmacia, Milton Keynes, UK) and the Mono Q column. The inhibitory effects of icariin on PDE5 and PDE4 activities were investigated by the two-step radioisotope procedure with [(3)H]-cGMP/[(3)H]-cAMP. Papaverine served as the control drug.
RESULTS:

Icariin and papaverine showed dose-dependent inhibitory effects on PDE5 and PDE4 activities. The IC(50) of Icariin and papaverine on PDE5 were 0.432 micromol/L and 0.680 micromol/L, respectively and those on PDE4, 73.50 micromol/L and 3.07 micromol/L, respectively. The potencies of selectivity of icariin and papaverine on PDE5 (PDE4/PDE5 of IC(50)) were 167.67 times and 4.54 times, respectively.
CONCLUSION:

Icariin is a cGMP-specific PDE5 inhibitor that may be developed into an oral effective agent for the treatment of ED. PMID:12646997

[medievil]

"Postsynaptic mechanisms are essential for forskolin-induced potentiation of synaptic transmission.
Sokolova IV, Lester HA, Davidson N.
Source
Department of Biology, California Institute of Technology, Pasadena, California, USA. irinas@ucla.edu
Abstract
It has been demonstrated that stimulation of protein kinase A (PKA) results in enhanced synaptic transmission in the hippocampus and other brain areas. To investigate mechanisms of the PKA-mediated potentiation of synaptic transmission, we used rat hippocampal embryonic cultures. In low-density cultures, paired recordings under the perforated patch demonstrated that 15-min forskolin treatment produced long-lasting potentiation of evoked excitatory postsynaptic currents (eEPSCs) mediated by the cAMP/PKA pathway. eEPSC amplitudes increased to 240 +/- 10% of baseline after 15 min of forskolin treatment (early). After forskolin washout, eEPSCs declined to a potentiated level. Potentiation was sustained for > or = 85 min after forskolin washout and, 60 min after forskolin washout, constituted 152 +/- 7% of baseline (late potentiation). Disruption of presynaptic processes with the whole cell configuration and internal solution containing PKA inhibitor peptide did not affect forskolin-induced potentiation. Disruption of postsynaptic processes, in contrast, impaired early potentiation and abolished late potentiation. Study of mEPSCs confirmed the contribution of postsynaptic mechanisms. Forskolin-induced enhancement of mEPSC frequency observed under the perforated patch was attenuated by the whole cell configuration. Forskolin also induced an increase of mEPSC amplitudes in the perforated patch, but not in the whole cell, experiments. Potentiation of eEPSCs was not activity dependent, persisting in the absence of stimulation. NMDA receptor blockade did not abolish forskolin-induced potentiation. In summary, we demonstrate that forskolin-induced potentiation of eEPSCs was mediated by postsynaptic mechanisms, presumably by upregulation of AMPA receptors by phosphorylation."

"It is thought that forskolin treatment induces cLTP by modulating or “sensitizing” the NMDARs so that spontaneous activity stimulates these receptors sufficiently to induce LTP. "

Potentiation of glutaminergic transmission makes me wonder wheter it would help anhedonia; effects on motivation; anxiety and focus have been reported; shizophrenia has learned us glutaminergic issues can be at the rootcause of reward related issues wich makes me wonder. This isnt allways the case but there's a group of mental disorders that highly relate to shizophrenia.

Edited by medievil, 24 May 2012 - 06:55 PM.

[vali]

My current stack, usually taken once in the morning, unless I forget:
3 grams piracetam
100mg choline
500mg ALCAR
3grams fish oil

120mg ginko
12 mg Forskolin
1 artichoke extract pill

Cambridge brain scores

Spatial search:
Taken 15 times without stack, scores of 6-8
Taken 4 times with stack, scores of 7-9

Spatial slider:
Taken 6 times without stack, average score of 70
Taken 4 times with stack, average scores of 90 (!!!)

I've taken other tests as well, but the stack doesn't seem to help with them. Or I simply haven't tested myself enough.

Subjectively, I feel a nice mood boost while on this drug.

Since I'm taking this stack with a bunch of racetams, I'm not certain how much of the effect comes from the LTP stack. All I know is racetams by themselves = good mood, along with the occasional mild mania, but NOT improved cambridge brain scores. Meanwhile, ginko/artichoke/forskolin by themselves had no effect at all on cambridge scores or mood. But put them together... That said, I've only taken this stack four times, so it's too early to say for certain that the higher scores are the result of the drugs, and not from more practice/placebo/vagaries of mood.

I'm still tinkering with the dosages of this stack, so we'll see. What sort of dosages is everyone else taking?

Edited by vali, 25 May 2012 - 01:15 AM.

[medievil]

http://www.frontiers...2011.00021/full

Also posted this in the other thread; vinpocetine is a available PDE1 inhibitor.

[summertimex]

wow this is sweet. i was looking into PDE4s and cAMP because of schizophrenia also. so i ordered artichoke and forskolin 2 days ago. i mostly have negative symptoms, well i got off the medicine around last october, then i was fine for a while from the 7 receptor upregulation, but then it downregulated as i got rejected in mid air. so i think my brain activated some kind of brain trauma depression from december to march. then i began to take supplements again and my cognition is much better but not where it was in december.

my current stack is:

GABA 1g
alpha-gpc 1-2g
inositol 3 g
calcium 600mg
magnesium 200mg
vitamin b complex
milk thistle extract
acai extract
vitamin c 1 g
vitamin e 800ui
fish oil with D3 2g
NAC 600mg
alpha-lipoic acid 400mg at night
blueberry extract 200mg
oxiracetam 800mg
aniracetam 2g twice a day
pramiracetam 1g
piracetam 2-3g
phosphatidylserine (sharp-ps) 3 at night but ran out recently
a protein bar
multivitamin

do you guys think the LTP lowers the threshold for psychosis after a certain point? or does it seem to be anti-psychotic in primitive mitochondrial modulatory capabilities?

well basically im left with anhedonia, floatiness, SA. so im working towards a 3-4 month slow thourough rebuild. caffeinated products are out of the question and when i drink green tea i see colors. or when i take focus factor and listen to binural beats i get syntesthesia and CEVs. im senstive to a lot of things its a very thin line to walk. like neuroinflammation from alchohol worsens it. so i cant do drugs anymore, but im doing some ibogaine TA for a "reset" soon.


well i think focus factor with its microdoses of multiple things like pyroglutamate and huperazine A plus all the minerals potentiates the racetams by a lot because that is one of the reasons my cognition was much better in december i was getting like As and Bs on economics quizzes unless i didnt take oxiracetam/alpha-gpc/focus factor. minerals just go hand in hand with conductivity.

also the racetam stack alleviated my "emotional lability" i was on a rollercoaster after the medicine.


i'll post what the CILTEP stack does to me. since i started taking all this stuff i felt my brain moving around probably creating dentrites and removing junk. so i am interested in its "regenerative" capability and receptor sentisization while bypassing dopamine chain stuff.

Edited by gen6k, 25 May 2012 - 08:15 AM.

[abelard lindsay]

You guys think that horny goat weed (icariins) could work as a PDE-4 inhibitor? I know it is supposed to act as a PDE-5 inhibitor.

It's been studied for it's effects as a PDE-4 inhibitor:

Yeah but if you look at the PDE4 ic50 you'll see that at 78ug Horny Goat Weed is a pretty weak PDE4 inhibitor and a much stronger PDE 5 inhibitor. Great for erections (Viagra is also a PDE5 inhibitor), but not for CILTEP. You're much better off sticking to Artichoke or Quercetin for CILTEP. Besides Forskolin + PDE5 inhibitor is not something I've researched. I have no idea what it will do and it won't produce the CILTEP effect.

"Postsynaptic mechanisms are essential for forskolin-induced potentiation of synaptic transmission.

NMDA receptor blockade did not abolish forskolin-induced potentiation. In summary, we demonstrate that forskolin-induced potentiation of eEPSCs was mediated by postsynaptic mechanisms, presumably by upregulation of AMPA receptors by phosphorylation."

"It is thought that forskolin treatment induces cLTP by modulating or "sensitizing" the NMDARs so that spontaneous activity stimulates these receptors sufficiently to induce LTP. "

I think the above study said NMDA receptors are not involved in Forskolin's activity, only AMPA receptors. If you want to play around with NMDA receptors you can try Magnesium Threonate.

Since I'm taking this stack with a bunch of racetams, I'm not certain how much of the effect comes from the LTP stack. All I know is racetams by themselves = good mood, along with the occasional mild mania, but NOT improved cambridge brain scores. Meanwhile, ginko/artichoke/forskolin by themselves had no effect at all on cambridge scores or mood. But put them together... That said, I've only taken this stack four times, so it's too early to say for certain that the higher scores are the result of the drugs, and not from more practice/placebo/vagaries of mood.

I'm still tinkering with the dosages of this stack, so we'll see. What sort of dosages is everyone else taking?

Well this is a pretty good stack because you've got the early LTP factors in there (ALCAR, Piracetam) and the late LTP factors (CILTEP). Awesome to see the scores! I usually take the brain challenge. I've gotten as high as 50 on this stack where I usually score in the mid to low 40s.

http://www.frontiers...2011.00021/full
Also posted this in the other thread; vinpocetine is a available PDE1 inhibitor.

AFAIK, PDE1 inhibition does not have a whole lot to do with LTP. I would avoid it with this stack.

wow this is sweet. i was looking into PDE4s and cAMP because of schizophrenia also. so i ordered artichoke and forskolin 2 days ago.
...
do you guys think the LTP lowers the threshold for psychosis after a certain point? or does it seem to be anti-psychotic in primitive mitochondrial modulatory capabilities?
...
caffeinated products are out of the question and when i drink green tea i see colors. or when i take focus factor and listen to binural beats i get syntesthesia and CEVs.

Caffeine is a broad PDE inhibitor. Someone who reacts badly to drinking caffeine might not be a good target for this stack. Also, aniraceam and CILTEP do not work well together because of LTP changing how Aniracetam interacts with AMPA receptors.

[summertimex]

yeah piracetam supposively doesn't increase NMDA receptor binding, maybe somewhat, but oxiracetam increases NMDA receptor density by 20% over time. what i found to be best for creativity is experiential-scaping on top of nootropic usage. well expressing different sorts of neurotransmissions and receptor binding. i find that nootropics without brain speed fluctuations doesn't ooze out as much profundity. yet nootropics are the best thing for assuredness of mental stability and the grinding of mediocre classes.

on the topic of LTP, many processes don't happen in the brain or are not at a psychoactive threshold of effect untill months after. so the LTP of LTP is probably something to be experienced down the line when the brain's neuroplastic tracks have finished opening previous channels. well its kind of like a cascading effect, or runners talk about how what you eat and your energy from last week effect next weeks race.

Edited by gen6k, 25 May 2012 - 09:54 AM.

[gizmobrain]

Yeah but if you look at the PDE4 ic50 you'll see that at 78ug Horny Goat Weed is a pretty weak PDE4 inhibitor and a much stronger PDE 5 inhibitor. Great for erections (Viagra is also a PDE5 inhibitor), but not for CILTEP. You're much better off sticking to Artichoke or Quercetin for CILTEP. Besides Forskolin + PDE5 inhibitor is not something I've researched. I have no idea what it will do and it won't produce the CILTEP effect.

Yeah, I was just responding to trip96's question about it. Plus, it gets included in some pro-energy supplements, so it's good to know what it does.

AFAIK, PDE1 inhibition does not have a whole lot to do with LTP. I would avoid it with this stack.

I haven't ever taken vinpocetine (well, I guess it was in a blend I was taking once), but it does effect LTP:

Eur J Pharmacol. 1992 Apr 29;215(1):17-22.
Effect of different subtypes of cognition enhancers on long-term potentiation in the rat dentate gyrus in vivo.

Molnár P, Gaál L.

Source

Department of Biochemistry, Chemical Works of Gedeon Richter Ltd., Budapest, Hungary.

Abstract

The effect of four drugs considered as cognition enhancers on the amplitude of the population spikes and on the long-term potentiation (LTP) evoked by perforant path stimulation was investigated in rat dentate gyrus in vivo. LTP was characterized by the absolute increase in the amplitude of the population spikes, which were expressed in mV, contrary to the widely used percentage value, because the absolute increase was independent of the pretetanus level, whereas the percentage increase was found to be negatively correlated with it. Intravenous administration of the drugs (piracetam 500 mg/kg, hydergine 2 mg/kg, vinpocetine 0.1 and 5 mg/kg and physostigmine 0.01 and 0.1 mg/kg) did not influence the amplitude of the population spikes itself. Piracetam and hydergine did not have an effect on LTP, while vinpocetine and physostigmine altered LTP in a similar manner. The higher doses of the two latter drugs, administered 5 min before tetanic stimulation, induced a significant potentiation of LTP, whereas a significant inhibition of LTP was obtained when the drugs were administered 30 min before tetanic stimulation. Based on the results obtained from guinea pig hippocampal slices, an LTP-potentiating effect of all compounds tested could have been anticipated, but this was not supported by our data. The apparent contradiction between the in vivo and in vitro results is discussed. PMID:1516646

Nihon Yakurigaku Zasshi. 1993 Sep;102(3):225-34.
[Pharmacology of long-term potentiation].

[Article in Japanese]
Satoh M, Watanabe S.

Source

Department of Molecular Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Japan.

Abstract

The physiological characteristics and significance of long-term potentiation in the hippocampus were summarized. In particular, it was pointed out that different mechanisms are involved in the production of hippocampal LTP between the mossy fiber-CA3 system and other systems such as Schaffer collateral-CA1, fimbrial fiber-CA3 and commissural/associational fiber-CA3. Furthermore, the epsilon-subspecies of protein kinase C (PKC) was demonstrated to be exclusively located at the presynaptic terminals in the hippocampus and activated by arachidonic acid, and this enzyme is suggested to be involved in the production of LTP through a phosphorylation of GAP-43, while the gamma-subspecies of PKC may be postsynaptically involved in LTP through an activation of NMDAR1. The production of LTP in the hippocampus is facilitated by many factors such as epidermal growth factor, fibroblast growth factors, somatostatin, M1 receptor agonists and many drugs like anirasetam, bifemelane, idebenone, indeloxazine and vinpocetine, but inhibited by M2-receptor agonists, scopolamine and midazolam. In addition to electrophysiological methods, LTP-like phenomena in 2-deoxyglucose uptake and leucine incorporation can be detected. These LTP phenomena in several animal models will be useful as indices for evaluating facilitatory actions of various compounds on learning/memory functions. PMID:8104851

There have been concerns about vinpocetine raised by others, but some people swear by it.

[Junk Master]

Just ordered some Forskolin and Quericin and will try with a low dose of Ropinirole.

[trip96]

I looked into quercetin and saw that tea is a great source of it. I know I may not be as knowledgable as most here but I hope to participate in this discussion. I drink about 4 cups of green day a day at least. Do any of you think that would be enough? Also with the tea you get theanine and caffeine which has been mentioned here as syngerstic. Any thoughts on this on this? I have a great variety of supplements at my disposal and I am currently in the hunt for artichoke. I made capsules with forskolin and horny goat weed and will post my experiences once I have enough time to really evaluate it. Thanks again guys this is a super interesting thread.