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  1. #1
    Senior Member FunkOdyssey's Avatar
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    I'm becoming interested in AChE inhibitors. They seem to be helpful in lyme-related long-term memory loss (I can barely remember anything about my adolesence and early 20's, its pretty sad). They seem to increase libido:

    <div class='quotetop'>QUOTE (rxlist.com)</div><div class='quotemain'>Adverse Effects Reported In Clinical Trials [for Donepezil]
    ....
    Nervous System: Frequent: delusions, tremor, irritability, paresthesia, aggression, vertigo, ataxia, increased libido</div>
    <div class='quotetop'>QUOTE (Brooklyn Tony)</div><div class='quotemain'>I bought some huperzine A today with 60 mg of ginko extract. I have used this a long time ago but forgot what effects it had upon me. My interest in using this again as a supplement stemmed from an article I read about this being a NDMA receptor antagonist.

    I took 100 mcg of the stuff (2 caps) and I feel the following:

    Very mentally sharp, effect took 20 mins
    Talkitive, I cant shut up! this is a good sup for socializing
    Not particulary anxious at all, even though I get bad anxiety with ginko sometimes (gingko doesnt do much for me)

    And I dont want to say it lifted the depression I got from the phenibut withdrawals but I feel pretty good.
    .....
    does anyone think because of these effects you can use huperzine off label as an antidepressant? ive been feeling pretty good the past few days, and my libido is higher than its been in a while</div>

    Huperzine and donepezil increase DA release in various ares of the brain (PMID: 16923332) and possibly NE as well (PMID: 7500384).

    Huperzine is also an NMDA antagonist and might help your brain survive DAA experimentation (PMID: 18588864 and PMID: 11825682). Even US Army researchers like it for this purpose (PMID: 11920920). Not just NMDA though, huperzine is broadly neuroprotective against a wide variety of insults (PMID: 15956816).

    Both huperzine (PMID: 10678121) and donepezil (PMID: 12105320) enhance memory and learning in healthy individuals, demonstrating a genuine nootropic effect.

    A couple people that liked donepezil, one you know, one you don't:

    <div class='quotetop'>QUOTE (Dopamine)</div><div class='quotemain'>Got the Donepezil yesterday afternoon. Took 5 mg. Early observations:

    - Increased self confidence
    - Slight dizziness
    - Senses much more "sensitive", i.e. noticing more details in physical objects
    - Increased irritability, more argumentative and hostile
    ...
    Donepezil seems also to potentiate my response to methylphenidate, another interesting observation.

    This is definetly something I would consider taking daily, as it feels like it is stimulating "central" structural regions of my brain.
    ...
    It's been almost a week now since I've consistently taken Donepezil at 5 mg in the morning. Something else I've noticed is that my sleep quality has greatly improved, and that I generally require about 1-2 hours less sleep per night.</div>
    <div class='quotetop'>QUOTE (utopizen @ dr-bob)</div><div class='quotemain'>One year on Aricept- ADD augmenter, sleep booster

    Posted by utopizen on May 25, 2006, at 16:21:57

    Yeah, just wanted to report my year now with a low dose (5mg) of Aricept.

    For one thing, why did I start it?

    I had social anxiety disorder really bad, along with ADD-inattentive subtype.

    I began reading journal articles in 2002 with doctors finding unique findings in patients with the combination of social anxiety disorder and ADD.

    Around the same time, the big Asperger's Syndrome push came around, trying to explain that you don't need to see Rain Man before diagnosing someone with Asperger's.

    Anyhow, I am on the following regimen:

    Klonopin Wafers (now generic!) 1mg 3x/day
    Desoxyn 5mg 2x/day
    Aricept 5mg/day
    Celexa 30mg/day
    Evoxac 30mg 3x/day (for dry mouth)
    Nexium 1x/day for GI side-effects of Aricept

    Side-effects:

    Well, I did attempt after a few months to go up to the regular dosing of 10mg (5mg is starting dose for geriatric patients).

    Long story short, I went manic for a few hours, it wasn't pleasant, but taking a Klonopin like with anything subdued the matter immediately.

    So I returned and stayed at 5mg.

    I was able to lower my dose to 5mg of Desoxyn 2x/day, while the average daily dose is 20-25mg/day.

    One thing I noticed when it began kicking in after a couple of months of being on it (2-3 months) was this incredibly refreshing sleep. The moment I awoke, whether it was a nap or during normal bedtime, I would find myself very restored.

    I also needed just 7 hours of sleep, and nothing more, to go all day long.

    I also had this sort of "automatic thinking" - I noticed it first when I awoke from a nap to a call, answered it, and the person on the other line said, "oh, I didn't mean to wake you" and I said "oh, no problem" all of a sudden energetically, and then he said something for a bit, and I spun off clearly and articulately (yet faster than I've ever talked) a few smoothly constructed sentences as though someone else had just written my response and orated it on my behalf.

    Well, I also managed to give presentations like this too-- concise, to-the-point, measured, quick-witted, and very cohesive. I just sort of would come in and out of topics with such ease.

    I even could exit gracefully (for the first time in my life) -- I would end the conversation I had to end by saying something very relevant to what had just been said by another person, and quickly cap it off with a "well, I have to go, but good to meet you, and we'll talk later" (an example) with no hesitation and total ease.

    Sounds oddly simple, but you have to understand the subtle nature of how smooth and effortless things like this became to me that were once incredibly difficult or frustrating.

    I felt like that kid in the movie Thumbsucker (2005) -- and I have tried every ADD stimulant, and nothing came close to what happened when I combined Aricept with a stimulant.

    Anyhow, hope everyone is well.

    By the way, my mood, and energy, and everything, has been rock solidly awesome for a year now.

    My doc over last summer, after a couple of months into regimen, said "This is the best I've ever seen you!"

    (I came to him a year earlier, despondent and so depressed I couldn't hide it at all to anyone).

    Take care!</div>

    Huperzine seems like almost a donepezil/memantine hybrid due to its unique pharmacology, except maybe better than memantine for cognition because it enhances rather than trashes cholinergic neurotransmission.

    Which drug is better, for specific indications and/or in general? Any updated experiences with either drug?
    "Also, can I rig some sort of enema out of household items?" -Tussman

    "I don't have the stamina for a 3-some, and I am a one-pump chump" -Ubiyca

  2. #2
    Senior Member KimberCT's Avatar
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    I really like Huperzine A. It gives me a very mellow feeling without being sedating.

    I've never used it for more than a day as I haven't had a chance to research its, or any other AChE inhibitor's, long term effects in health individuals.

    Think I'll actually take some tonight before doing some reading...

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    I prefer Huperzine over Donepezil. However both make me feels grumpy and somewhat agitated after chronic dosing. This is even in conjunction with an antidepressant.

    Be careful with these types of drugs. That utopizen guy eventually quit using donepezil because it turned him into a manic asshole. I felt the same kind of feelings coming on and was self-aware enough to dc them before I did any damage in my life.

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    I similarly wonder about the restorative merits of Aricept, especially given it is one of a handful of medications known to moonlight as a potent sigma 1 agonist (14.6nM).

    http://www.ncbi.nlm.nih.gov/pubmed/18571635

    Donepezil is a potent acetylcholinesterase inhibitor used for the treatment of Alzheimer's disease. Although acetylcholinesterase inhibitors are thought to be symptomatic treatment of Alzheimer's disease, it is not clear whether they are effective against progressive degeneration of neuronal cells. In this study, we investigated the neuroprotective effects of donepezil against ischemic damage, N-methyl-d-aspartate (NMDA) excitotoxicity, and amyloid-beta (Abeta) toxicity using rat brain primary cultured neurons. Lactate dehydrogenase (LDH) released into the culture medium was measured as a marker of neuronal cell damage. As an ischemic damage model, we used oxygen-glucose deprivation in rat cerebral cortex primary cultured neurons. Pretreatment with donepezil (0.1, 1 and 10 microM) significantly decreased LDH release in a concentration-dependent manner. However, other acetylcholinesterase inhibitors (galantamine, tacrine and rivastigmine) did not significantly decrease LDH release. In a NMDA excitotoxicity model, pretreatment with donepezil (0.1, 1 and 10 microM) decreased the LDH release in a concentration-dependent manner. In binding assay for glutamate receptors, donepezil at 100 microM only slightly inhibited binding to the glycine and polyamine sites on NMDA receptor complex. We further examined the effect of donepezil on Abeta (1-40)- and Abeta (1-42)-induced toxicity in primary cultures of rat septal neurons. Pretreatment with donepezil (0.1, 1 and 10 microM) significantly decreased LDH release induced by Abetas in a concentration-dependent manner. However, other acetylcholinesterase inhibitors (galantamine and tacrine) and NMDA receptor antagonists (memantine and dizocilpine (MK801)) did not significantly decrease LDH release. These results demonstrate that donepezil has protective effects against ischemic damage, glutamate excitotoxicity and Abeta toxicity to rat primary cultured neurons and these effects are not dependent on acetylcholinesterase inhibition and antagonism of NMDA receptors. Thus, donepezil is expected to have a protective effect against progressive degeneration of brain neuronal cells in ischemic cerebrovascular disease and Alzheimer's disease.

    In the present study, we examined the interaction of (+/-)-2,3-dihydro-5,6-dimethoxy-2-[[1-(phenylmethyl)-4-piperidinyl]-methyl]-1H-inden-1-one hydrochloride (donepezil), a potent cholinesterase inhibitor, with two additional therapeutically relevant targets, N-methyl-d-aspartate (NMDA) and sigma(1) receptors. Donepezil blocked the responses of recombinant NMDA receptors expressed in Xenopus oocytes. The blockade was voltage-dependent, suggesting a channel blocker mechanism of action, and was not competitive at either the l-glutamate or glycine binding sites. The low potency of donepezil (IC(50) = 0.7-3 mM) suggests that NMDA receptor blockade does not contribute to the therapeutic actions of donepezil. Of potential therapeutic relevance, <u>donepezil binds to the sigma(1) receptor with high affinity (K(i) = 14.6 nM)</u> in an in vitro preparation (Neurosci Lett 260:5-8, 1999). Thus, we sought to determine whether an interaction with the sigma(1) receptor may occur in vivo under physiologically relevant conditions by evaluating the sigma(1) receptor dependence effects of donepezil in behavioral tasks. Donepezil showed antidepressant-like activity in the mouse-forced swimming test as did the sigma(1) receptor agonist igmesine. This effect was not displayed by the other cholinesterase inhibitors, rivastigmine and tacrine. The donepezil and igmesine effects were blocked by preadministration of the sigma(1) receptor antagonist N-[2-(3,4-dichlorophenyl)ethyl]-N-methyl-2-(dimethylamino) ethylamine (BD1047) and an in vivo antisense probe treatment. The memory-enhancing effect of donepezil was also investigated. All cholinesterase inhibitors attenuated dizocilpine-induced learning impairments. However, only the donepezil and igmesine effects were blocked by BD1047 or the antisense treatment. Therefore, <u>donepezil behaved as an effective sigma(1) receptor agonist on these behavioral responses, and an interaction of the drug with the sigma(1) receptor must be considered in its pharmacological actions.</u>

    A poster named Atreyu posted a similar experience to Utopizen on dr.bob (Positive experience with Aricept as part of a vast regimen), and it remains to be seen if he is observing continued success with this. The one other post of his I was able to locate on dr.bob (which he posted 4 months later), didn't indicate if he was still using Aricept but did state he had swapped antipsychotics and his writing style in this post also alluded to the possibility of mania. I'd be quite interested to see a recent follow-up post from this individual - He too was taking 5mg.

    http://www.dr-bob.org/babble/20070219/msgs/734959.html
    http://www.dr-bob.org/babble/20070219/msgs/734959.html




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    The differences in pharmacology between the two have been well elucidated by the OP, but a couple of other distinctions come to mind -

    Research - Donepezil has been studied much more extensively, and the research itself comes from relatively reputable sources. A cursory glance at PubMed reveals that 380 clinical trials have been conducted in some form or another; whereas with Huperzine A, there have only been 9 such studies. So, the amount of research alone clearly favors Donepezil.

    Metabolism - Donepezil interacts extensively with CYP3A4 and CYP2D6, and is bound to plasma at a rate of 96% (12162759), increasing the risks for interaction with other medications. Huperzine A, however, does not affect cytochrome P-450 levels (in rats) at "pharmalogical dose(s)" of 0.1 mg/kg (12904285).

    It's an interesting topic that merits further discussion. Personally, I favor Donepezil, but certainly don't discount Huperzine A.
    "When men are most sure and arrogant they are commonly most mistaken, giving views to passion without that proper deliberation which alone can secure them from the grossest absurdities." - David Hume

  6. #6
    Senior Member FunkOdyssey's Avatar
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    Hey Medieval, donepezil helped a guy's social anxiety and ADD, when are you going to add it to your stack?
    "Also, can I rig some sort of enema out of household items?" -Tussman

    "I don't have the stamina for a 3-some, and I am a one-pump chump" -Ubiyca

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    Senior Member FunkOdyssey's Avatar
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    I wonder if AChE inhibition contributes to the observed effects of icariin on libido?



    Brain Res. 2010 Jun 2;1334:73-83. Epub 2010 Apr 7.

    Neuroprotective effects of icariin on memory impairment and neurochemical deficits in senescence-accelerated mouse prone 8 (SAMP8) mice.



    He XL, Zhou WQ, Bi MG, Du GH.



    Research Center for Pharmacology and Toxicology, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.

    Abstract



    The senescence-accelerated mouse prone 8 (SAMP8) is a novel aging model characterized by early onset and rapid advancement of senescence. In the present study, 6-month-old male SAMP8 mice were orally administered icariin (75, 150mg/kg) for 15weeks. Mice were submitted to passageway water maze test and step-down passive avoidance test for evaluating cognitive impairments. The HPLC-EC technique was used to determine the monoamine contents in the brain. The effects of icariin on oxidative stress and the acetylcholinesterase (AChE) activity of SAMP8 mice were also investigated. We found that icariin treatment significantly prevented learning and memory impairments of SAMP8 mice in passageway water maze test and step-down test. Icariin could partly reverse alterations of monoamines and metabolites levels in the cortex and hippocampus of SAMP8 mice. Furthermore, icariin-treated SAMP8 mice had significantly decreased malondialdehyde (MDA), nitric oxide (NO) contents, lowered nitric oxide synthase (NOS) activity and higher glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities in the brain homogenates and serum. Meanwhile, the acetylcholinesterase activity was markedly inhibited after icariin administration. However, the positive control piracetam did not show significant beneficial effects. In conclusion, the present findings demonstrated that the improvement of icariin on cognitive impairments in SAMP8 mice may be due to increasing monoamines levels, inhibiting oxidative damage and decreasing acetylcholinesterase activity.

    Copyright 2010
    "Also, can I rig some sort of enema out of household items?" -Tussman

    "I don't have the stamina for a 3-some, and I am a one-pump chump" -Ubiyca

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    be careful to keep your choline intake to a minimum. I have found that AchE inhibitors work wonderfully on their own, but whenever I combine them any form of choline (be it choline bitartrate, Alpha-GPC, or even a few eggs for that matter) I get symptoms of too much Acetylcholine ( muscle tension and depression being the most unpleasant)

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    Is anyone currently on donepzil? I am considering giving it a go. I don't really feel or get much from hyperzine a apart from nausea and headache.

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    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by anito View Post
    Is anyone currently on donepzil? I am considering giving it a go. I don't really feel or get much from hyperzine a apart from nausea and headache.
    For what it's worth, it was just shown to [I]impair/i] cognition in healthy older adults. I don't have the study now, but it's not looking like a particularly compelling drug these days if you don't have Alzheimer's.

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    Quote Originally Posted by Ex Dubio View Post
    For what it's worth, it was just shown to [I]impair/i] cognition in healthy older adults. I don't have the study now, but it's not looking like a particularly compelling drug these days if you don't have Alzheimer's.
    There's actually a decent amount of evidence for both improving and impairing cognition. There was one study out there that had a table summarizing all the research results so far but I don't have it anymore.

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    Senior Member Ex Dubio's Avatar
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    Quote Originally Posted by sterling100 View Post
    There's actually a decent amount of evidence for both improving and impairing cognition. There was one study out there that had a table summarizing all the research results so far but I don't have it anymore.
    I knew about the evidence suggesting it improves cognition, but hadn't seen previous results suggesting the contrary. I thought it was well-established that AChE inhibitors improve cognition, albeit at the price of a wicked side effect profile. But apparently it's more nuanced than that...

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    Quote Originally Posted by Ex Dubio View Post
    I knew about the evidence suggesting it improves cognition, but hadn't seen previous results suggesting the contrary. I thought it was well-established that AChE inhibitors improve cognition, albeit at the price of a wicked side effect profile. But apparently it's more nuanced than that...
    Ok I found that one study again, and only two studies in their table showed a negative effect. Most of them were positive, and a couple showed neutral results. I think that in general what you were saying is correct. I'll have to scan through everything again to see if I can find out why I remembered there being a decent amount of evidence for the negative effects, versus just a little bit.

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    Quote Originally Posted by Ex Dubio View Post
    For what it's worth, it was just shown to [I]impair/i] cognition in healthy older adults. I don't have the study now, but it's not looking like a particularly compelling drug these days if you don't have Alzheimer's.
    Never got the chance to read this before i made a purshace. It's hella expensive too, i can't surely ditch it in the bin. I have hyperzine a and i don't think they have impaired my cognition, strange that donepzil will.

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    Senior Member FunkOdyssey's Avatar
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    Quote Originally Posted by anito View Post
    Never got the chance to read this before i made a purshace. It's hella expensive too, i can't surely ditch it in the bin.
    Loss aversion and the sunk cost fallacy
    "Also, can I rig some sort of enema out of household items?" -Tussman

    "I don't have the stamina for a 3-some, and I am a one-pump chump" -Ubiyca

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    This table is pretty awesome. Notice that all the acute studies lasting only one day showed improvement.

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    Quote Originally Posted by sterling100 View Post
    This table is pretty awesome. Notice that all the acute studies lasting only one day showed improvement.
    so it looks the positives outweigh the negatives. But it still sucks in can impair. I mean what if it does impair you and you actually don't recover, ops. Spent $70 on it, mad.

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    Quote Originally Posted by FunkOdyssey View Post
    Yupp i am guilty. How do i get out of it?

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    Quote Originally Posted by anito View Post
    Yupp i am guilty. How do i get out of it?
    ...CBT?

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