# Why aren't there any meds that increase acetylcholine?



## kintrovert (Oct 28, 2005)

From what I've read, acetylcholine can be a crucial neurotransmitter that benefits cognitive function, memory...and even anxiety and depression. Right now I seem to be on the acetylcholine bandwagon...but I'm disappointed that, amidst the slew of drugs that address serotonin, or serotonin/norephinephrine, or dopamine...there doesn't seem to be a drug that addresses acetylcholine. Or is there?

The drugs I've heard of that deal with acetylcholine seem to be made/marketed for Alzheimer's patients - there seem to be none that are geared toward the purely psychiatric patient.

I have a slew of cognitive issues that seem to be a byproduct of my mental illness(es) (and/or the drugs I've taken over the years), I have a _severe_ inability to handle even slight stress...and dammit - acetylcholine just _may_ be a neurotransmitter that can ease my problems. Acetylcholine may be better for me than dopamine...yet, there is nothing out there for me to try?


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## Broshious (Dec 23, 2006)

You might try three things.

One, take a choline supplement.

Two, try DMAE, _"Another point that will shock you is the fact that it is even better than taking Choline in its pure form. Scientists believe this is due to the fact that DMAE inhibits the breakdown of Choline."_

Three, try taking piracetam, or some of the other racetams too if you're interested, _"Piracetam improves the function of the neurotransmitter acetylcholine via muscarinic cholinergic (ACh) receptors which are implicated in memory processes."_


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## korey (Apr 25, 2006)

Just because a medication has a target demographic (ie, people with Alzheimer's) doesn't mean that its use can't be employed to treat other conditions. I'm not entirely sure how Alzheimer's medications work, but if they improve the effectiveness/concentration/amount of ACh in the brain without debilitating side-effects, then why not ask your doctor about trying one of them? My psychiatrist treats Alzheimer's patients (There are little strategically-placed Namenda advertisements all over his office), so it's not something restricted to neurologists.

The only drawback would be that Alzheimer's meds are probably very expensive, so unless you have good insurance, then you might want to look into the supplements mentioned above.


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## korey (Apr 25, 2006)

Hmm... It seems that Namenda can also be used to treat depression and pain disorders because it's an NMDA antagonist (so it doesn't seem to affect ACh). However, there are medications like Aricept and Reminyl that act as acetylcholinesterase inhibitors (ie, they slow the metabolic breakdown of ACh). Some MAOI's are used for the same reason (like Azilect and EMSAM), but MAOI's can come with hefty liabilities if you're not careful.

I did come across one medication called Elen (indeloxazine) that is used to treat both depression and Alzheimer's. It does so by actually releasing serotonin and ACh in the brain, and then some additional serotonergic and norepinephrinergic action to help with depression (I'm assuming). It seems like a good thing to look into being as it actually releases more ACh into your brain rather than slowing the breakdown of the ACh that is already there.


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## Broshious (Dec 23, 2006)

korey said:


> I did come across one medication called Elen (indeloxazine) that is used to treat both depression and Alzheimer's. It does so by actually releasing serotonin and ACh in the brain, and then some additional serotonergic and norepinephrinergic action to help with depression (I'm assuming). It seems like a good thing to look into being as it actually releases more ACh into your brain rather than slowing the breakdown of the ACh that is already there.


From what I read they believe its ACh effects are related to its effects on 5-HT4 as 5-HT4 antagonists significantly inhibited the ACh release. The only problem is that the study showed that citalopram(an SSRI) also increased ACh output so it may very well merely be an effect of its serotonin reuptake inhibition. I only have access to the abstract so I was not able to get any numbers to see if indeloxazine was more efficient at increasing ACh release. I would think it may be more potent as they showed that by depleting serotonin levels the level of ACh release was reduced, and indeloxazine increases 5-HT release(wish I had some numbers on how much it does this).

Seeing as how 5-HT4 receptors seem to be responsible for ACh release one might look into specific 5-HT4 agonists. Interestingly enough there is a 5-HT4 agonist(RS6733) currently in development which for use as a rapid acting antidepressant(YeeHaw), nootropic, and treatment for Alzheimer's. There are some 5-HT4 agonists currently available as well.

Just saw this about RS67333 and prucalopride(another 5-HT4 agonist):

_"They found that both 5-HT4 agonists significantly reduced the time of immobility by about 50% compared with controls, whereas citalopram reduced immobility time by about 23%"_

_"In addition, three days of treatment also significantly promoted neurogenesis in the subgranular zone of the dentate gyrus of the hippocampus, an effect normally seen after a minimum of two weeks of treatment with classical antidepressants or SSRIs."_

_"In behavioral experiments, RS 67333 was significantly more effective than citalopram at suppressing activity in a rat model of hyperlocomotion"_

_"Expression of 5-HT4 receptors in the prefrontal cortex and hippocampus is associated with increased learning, memory, and cognition, another potential beneficial effect of 5-HT4 agonists."_

_Dr. Duman also noted, however, that because 5-HT4 receptors are also expressed in the gastrointestinal system and the heart, 5-HT4 agonists could have unforeseen adverse effects."_

5-HT4 agonists have been looked into for treatment for IBS. A study on prucalopride seemed to point to it lacking negative heart effects due to it only being a partial agonist for the 5-HT4 receptors in the heart while being a full agonist in the GI tract and the brain. It looks like a winner to me so far.

Unfortunately:

_"However, when the authors compared RS 67333 with fluoxetine (Prozac) in rat models of anxiety, they found that neither agent had a significant effect."_


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## kintrovert (Oct 28, 2005)

Broshious said:


> You might try three things.
> 
> One, take a choline supplement.
> 
> ...


Thanks for this...but from my (admittedly limited) experience and from reading other people's experiences, supplements "poop out" after a short time. I'd love to try these and I just might (or probably will)....but it's as if these supplements have already broken my heart before I've even tried them - because of the likelihood that I'll feel a difference for a short time before the supplement "betrays" me by failing to be effective anymore.

At least meds (seem to) remain effective for a longer time before they start "pooping out", as well...

(Around the same time I started this thread, I started another acetylcholine-related thread in the "Nutrition, Supplements and Excercise" forum in which I mention my concerns about supplements being so "fickle" in their long-term effectiveness.)


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## kintrovert (Oct 28, 2005)

korey said:


> Just because a medication has a target demographic (ie, people with Alzheimer's) doesn't mean that its use can't be employed to treat other conditions. I'm not entirely sure how Alzheimer's medications work, but if they improve the effectiveness/concentration/amount of ACh in the brain without debilitating side-effects, then why not ask your doctor about trying one of them? My psychiatrist treats Alzheimer's patients (There are little strategically-placed Namenda advertisements all over his office), so it's not something restricted to neurologists.
> 
> The only drawback would be that Alzheimer's meds are probably very expensive, so unless you have good insurance, then you might want to look into the supplements mentioned above.


Good points...I thought about this, but I'm wondering if - since Alzheimer's patients probably have a more severe acetylcholine deficiency and their disease physiology is different - if these meds would be too "strong", or otherwise inappropriate. Maybe a low dose would work...it's definitely an intriguing quandry.


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## kintrovert (Oct 28, 2005)

Korey and Broshious, thank you both for the interesting, hard-core drug info. This is really something to look into - that is, if I'm willing to become even more of a human experiment than I have been over the past 13 years....and _if_ I could feasibly pull this off with the (limited) resources that are available to me. But the risks may be worth it.


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## Broshious (Dec 23, 2006)

kintrovert said:


> Korey and Broshious, thank you both for the interesting, hard-core drug info. This is really something to look into - that is, if I'm willing to become even more of a human experiment than I have been over the past 13 years....and _if_ I could feasibly pull this off with the (limited) resources that are available to me. But the risks may be worth it.


Let us know if you find out anything nifty.

Someone mentioned Acetyl-L-Carnitine in your other thread so I thought I'd mention it here:

_"The acetyl group of acetyl l carnitine is used to form acetyl-CoA."

"Choline, in combination with Acetyl-CoA is catalyzed by the enzyme choline acetyltransferase to produce acetylcholine and a coenzyme a byproduct."_

This is a study done in rats:

_"Our data suggest that chronic Acetyl-L-carnitine administration may produce an inverted U-shaped curve of dose-dependent changes in anxiety-like behaviour."_

Another supplement for acetylcholine is Huperzine A:

"Huperzine A is a potent plant-based alkaloid with reversible acetylcholinesterase-inhibitory action isolated from the Chinese club moss."

Here's two more Magnolol and Honokiol:

"Other studies have shown that magnolol and honokiol modulate the activity of various neurotransmitters and related enzymes in the brain, by increasing choline acetyltransferase activity, inhibiting acetylcholinesterase, and increasing acetylcholine release-all important in supporting normal brain function, and especially in protecting the brain from Alzheimer's disease."

"A similar test found that honokiol significantly prolonged the time the animals spent in a maze, suggesting an anti-anxiety effect. Normally, when rodents are placed in a maze, they like to hide and not explore because they get anxious. These rodents appeared to be more relaxed, and expressed curiosity about their environment. When the animals were given honokiol in various doses over a period of seven days, the effects remained the same: there was no change in motor activity or in the animals' performance. The animals receiving the diazepam (Valium), however, became dependent on the same dose, which hindered their performance."

That's all for now


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## korey (Apr 25, 2006)

Yes, do keep us informed. Wouldn't it be strange if the next wave of popular psychiatric medications were derived from Alzheimer's medications? :b Well, I suppose it wouldn't be that strange. The first SSRI (not Prozac) was derived from chlorpheniramine, which is an antihistamine found in lots of over-the-counter allergy medicines today. Lots of antinausea medications are derived from the same compound that older antipsychotics are derived from. Psych meds seem to be hiding in the weirdest places.


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## Broshious (Dec 23, 2006)

korey said:


> Yes, do keep us informed. Wouldn't it be strange if the next wave of popular psychiatric medications were derived from Alzheimer's medications? :b Well, I suppose it wouldn't be that strange. The first SSRI (not Prozac) was derived from chlorpheniramine, which is an antihistamine found in lots of over-the-counter allergy medicines today. Lots of antinausea medications are derived from the same compound that older antipsychotics are derived from. Psych meds seem to be hiding in the weirdest places.


If I'm not mistaken the development of Prozac came from Benadryl's(Diphenhydramine) SSRI effects as well.


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## korey (Apr 25, 2006)

Broshious said:


> korey said:
> 
> 
> > Yes, do keep us informed. Wouldn't it be strange if the next wave of popular psychiatric medications were derived from Alzheimer's medications? :b Well, I suppose it wouldn't be that strange. The first SSRI (not Prozac) was derived from chlorpheniramine, which is an antihistamine found in lots of over-the-counter allergy medicines today. Lots of antinausea medications are derived from the same compound that older antipsychotics are derived from. Psych meds seem to be hiding in the weirdest places.
> ...


Yes indeed  The one I was referring to was zimelidine. It was banned worldwide due to some really unpleasant side effects.
http://pubchem.ncbi.nlm.nih.gov/summary ... sid=182628

Luvox and Prozac came soon after zimelidine was stricken down.


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## kintrovert (Oct 28, 2005)

Broshious said:


> kintrovert said:
> 
> 
> > Korey and Broshious, thank you both for the interesting, hard-core drug info. This is really something to look into - that is, if I'm willing to become even more of a human experiment than I have been over the past 13 years....and _if_ I could feasibly pull this off with the (limited) resources that are available to me. But the risks may be worth it.
> ...


Thanks for this - wow...choices, choices. Options and more options. Which is a good thing, but for someone who can be overwhelmed doing simple grocery shopping -making a clear choice on the options presented to me is daunting!

So does the passage "Our data suggest that chronic Acetyl-L-carnitine administration may produce an inverted U-shaped curve of dose-dependent changes in anxiety-like behaviour." mean that acetyl-l-carnitine is more effective at either low or high doses - and the mid-range doses yield no effect?


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## kintrovert (Oct 28, 2005)

Broshious said:


> korey said:
> 
> 
> > I did come across one medication called Elen (indeloxazine) that is used to treat both depression and Alzheimer's. It does so by actually releasing serotonin and ACh in the brain, and then some additional serotonergic and norepinephrinergic action to help with depression (I'm assuming). It seems like a good thing to look into being as it actually releases more ACh into your brain rather than slowing the breakdown of the ACh that is already there.
> ...


I wanted to ask a question regarding this information...is it correct to interpret the above info to mean that SSRIs (or similar drugs that raise serotonin) also work to increase acetylcholine within the brain? Is this why, when I stopped taking Effexor - my cognitive function greatly suffered? I think I've been on a steady cognitive decline for many years...but when I stopped taking Effexor several months ago - there seemed to be a drastic, more sudden change in my mental function. I simply cannot think well - words don't come easily (if at all), "higher" mental functions don't seem to be working well (such as insight and judgement). If someone asks me to recall details of a conversation, I'm unable to do (verbalize) it. My concentration is even worse than before. My thinking is much "slower"...as if I'm slogging through mud. I'm having all kinds of mental issues (in addition to all the prerequisite mood problems).

Before - I seemed to suffer depression and anxiety without all of these accompanying cognitive issues (or at least these problems were much milder) - but in recent years, the cognitive issues have been as bad as the emotional suffering. What's going on? Is it irreversible brain-damage? Is it an acetylcholine issue?


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## Broshious (Dec 23, 2006)

kintrovert said:


> I wanted to ask a question regarding this information...is it correct to interpret the above info to mean that SSRIs (or similar drugs that raise serotonin) also work to increase acetylcholine within the brain? Is this why, when I stopped taking Effexor - my cognitive function greatly suffered? I think I've been on a steady cognitive decline for many years...but when I stopped taking Effexor several months ago - there seemed to be a drastic, more sudden change in my mental function. I simply cannot think well - words don't come easily (if at all), "higher" mental functions don't seem to be working well (such as insight and judgement). If someone asks me to recall details of a conversation, I'm unable to do (verbalize) it. My concentration is even worse than before. My thinking is much "slower"...as if I'm slogging through mud. I'm having all kinds of mental issues (in addition to all the prerequisite mood problems).
> 
> Before - I seemed to suffer depression and anxiety without all of these accompanying cognitive issues (or at least these problems were much milder) - but in recent years, the cognitive issues have been as bad as the emotional suffering. What's going on? Is it irreversible brain-damage? Is it an acetylcholine issue?


I'm no doctor, but Effexor also effects Norepinephrine(NE), assuming you had a high enough dose of course. There are NE meds specifically designed for ADD so that could also be something to look into.

I wouldn't be worried about brain damage. I'm sure you'll be able to fix the problem if you can just find the right meds/supplements.


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## kintrovert (Oct 28, 2005)

Broshious said:


> I'm no doctor, but Effexor also effects Norepinephrine(NE), assuming you had a high enough dose of course. There are NE meds specifically designed for ADD so that could also be something to look into.
> 
> I wouldn't be worried about brain damage. I'm sure you'll be able to fix the problem if you can just find the right meds/supplements.


Yeah, Effexor supposedly also works on NE - supposedly at doses greater than 150mg/day. They say that for doses smaller than 150mg, it acts more as a SSRI (only raising serotonin). I was on a high (300mg/day) dose of Effexor for my first two years on this med - but I spent the majority of my Effexor years taking 150mg/day. So I'm not certain if I was getting a significant NE boost on 150mg - although the fact that the med didn't "poop out" on me as much as my previous meds Prozac and Luvox may indicate that Effexor was working in a different manner (whether that "different manner" was greater NE boosting or something else...who knows?).

I have questions about the actual helpfulness of boosting NE, anyway. It seems as though, for people (such as myself) who are suffering from severe anxiety - that NE would hurt, instead of help. Anxiety is an exagerrated "fight or flight" reaction - and NE is supposedly the "fight or flight" neurotransmitter. Our problem is that we may already have too _much_ NE, or that our brains may be overly sensitive to NE.

But I notice that so many meds raise NE in addition to serotonin - it's as if NE is an extremely "easy" neurotransmitter to boost. There seem to be precious few meds that boost dopamine - and dopamine may be more helpful to us than NE. (In my view, dopamine may give us more energy and alertness without making us as agitated and jittery. That's just my "edjucated guess" based on what I've read - I don't think I've seen any explicit statements making this comparison between dopamine and NE.) Same with acetylcholine (aCH) - aCH may be more useful to many of us than NE.


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## Broshious (Dec 23, 2006)

kintrovert said:


> I have questions about the actual helpfulness of boosting NE, anyway. It seems as though, for people (such as myself) who are suffering from severe anxiety - that NE would hurt, instead of help. Anxiety is an exagerrated "fight or flight" reaction - and NE is supposedly the "fight or flight" neurotransmitter. Our problem is that we may already have too _much_ NE, or that our brains may be overly sensitive to NE.
> 
> But I notice that so many meds raise NE in addition to serotonin - it's as if NE is an extremely "easy" neurotransmitter to boost. There seem to be precious few meds that boost dopamine - and dopamine may be more helpful to us than NE. (In my view, dopamine may give us more energy and alertness without making us as agitated and jittery. That's just my "edjucated guess" based on what I've read - I don't think I've seen any explicit statements making this comparison between dopamine and NE.) Same with acetylcholine (aCH) - aCH may be more useful to many of us than NE.


Try taking Ritalin sometime, it works pretty well until it runs out, and then I usually feel pretty craptastic. I think Adderall is great for social anxiety. It not only removes the anxiety, but it tends to make you WANT to talk to people. Dexedrine would probably be even better, and I think Desoxyn would work incredibly well.

I suppose these could be combined with a benzo for when the medicine is wearing off so you don't feel so ****ty and you can get some sleep. Although I have no idea if that kind of thing would work long term or not.


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## korey (Apr 25, 2006)

Broshious said:


> Try taking Ritalin sometime, it works pretty well until it runs out, and then I usually feel pretty craptastic. I think Adderall is great for social anxiety. It not only removes the anxiety, but it tends to make you WANT to talk to people. Dexedrine would probably be even better, and I think Desoxyn would work incredibly well.
> 
> I suppose these could be combined with a benzo for when the medicine is wearing off so you don't feel so @#%$ and you can get some sleep. Although I have no idea if that kind of thing would work long term or not.


I take a dose of Adderall and a dose of Xanax in the morning before school (along with the rest of my morningly meds), and they balance each other pretty well. The Adderall is pretty much out of my system by night, so a "come down" med isn't necessary. Chronic amphetamine users are known to use benzos when they "come down", though. :um


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