Any easy to find supplements or medications that are IDO and TDO inhibitors ?

[Nas]

Any easy to find supplements or medications that are IDO and TDO inhibitors  ?

[Quantum]

Hi Nas,

For IDO inhibitors: 

https://en.wikipedia.org/wiki/Indoleamine_2,3-dioxygenase#Inhibitors

rosmarinic acid, mentioned in the link above, can be found in many supplements, as listed here: https://en.wikipedia.org/wiki/Rosmarinic_acid#Natural_occurrences 



For TDO inhibitors:

Harder to find a list, I have found the natural ones I know by searching a lot. 

For quercetin: http://www.ncbi.nlm.nih.gov/pubmed/24269239 and other references.


You can find article on single compound, like allopurinol, a prescription drug that has TDO inhibitor properties:

http://www.sciencedirect.com/science/article/pii/S0091305715300678 and

https://www.researchgate.net/publication/259959251_Inhibition_of_stress-induced_hepatic_tryptophan_23-dioxygenase_exhibits_antidepressant_activity_in_an_animal_model_of_depressive_behaviour

There is also an interesting by-pass:  if you know that xanthine oxydase inhibitors are usually good TDO inhibitors, you can find a list at https://en.wikipedia.org/wiki/Xanthine_oxidase_inhibitor ( you will see that allopurinol is there, of course, but quercetin, and also propolis, and other less known natural products)


You can also search in articles on sites like https://www.ncbi.nlm.nih.gov/pubmed/?term=tdo+inhibitors or https://newdrugapprovals.org/tag/ido1-and-tdo-inhibitors/ 



Big Pharma are after IDO and TDO inhibitors, for cancer treatment mostly, and for depression too, but they still are in pre-clinical research. For examples of current prospects in the pharmaceutical pipeline, see http://www.nature.com/nbt/journal/v33/n4/fig_tab/nbt0415-321_T1.html

[Quantum]

Some interesting quotes from the last link mentioned in my previous post, http://www.nature.com/nbt/journal/v33/n4/fig_tab/nbt0415-321_T1.html :

If anyone believes that there is auto-immunity and inflammation in POIS, then:

" IDO1 and IDO2 are implicated in inflammatory diseases. IDO1 knock-out mice don’t manifest spontaneous disorders of classical inflammation and existing known small molecule inhibitors of IDO do not elicit generalized inflammatory reactions (Prendergast et al. Curr Med Chem. 2011; 18(15):2257-62). Rather, IDO impairment alleviates disease severity in models of skin cancers promoted by chronic inflammation, inflammation-associated arthritis and allergic airway disease. Moreover, IDO2 is a critical mediator of autoantibody production and inflammatory pathogenesis in autoimmune arthritis. IDO2 knock-out mice have reduced joint inflammation compared to wild-type mice due to decreased pathogenic autoantibodies and Ab-secreting cells (Merlo et al. J. Immunol. (2014) vol. 192(5) 2082-2090). Thus, inhibitors of IDO1 and IDO2 are useful in the treatment of arthritis and other inflammatory diseases."


and, another reason to reduce sugars in POIS ( this reminds me of b_jim recent post about taking sugar and noticing increase POIS symptoms after... if kynurenines are indeed one of the causes of POIS cogitive symptoms, then taking sugar increase their toxicity, so it increases POIS symptoms ):

"     Several studies have found Kynurenine pathway metabolites to be neuroactive and neurotoxic. Neurotoxic kynurenine metabolites are known to increase in the spinal cord of rats with experimental allergic encephalomyelitis (Chiarugi et al., Neuroscience, 2001, 102(3):687-95). The neurotoxic effects of Kynurenine metabolities is exacerbated by increased plasma glucose levels. Additionally, changes in the relative or absolute concentrations of the kynurenines have been found in several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease and Parkinson’s disease, stroke and epilepsy (Németh et al., Central Nervous System Agents in Medicinal Chemistry, 2007, 7:45-56; Wu et al. 2013; PLoS One; 8(4)). "

and finally, what I think is also relevant for POIS:

  " Neuropsychiatric diseases and mood disorders such as depression and schizophrenia are also said to have IDO1 and Kynurenine dysregulation. Tryptophan depletion and deficiency of neurotransmitter 5-hydroxytryptamine (5-HT) leads to depression and anxiety. Increased IDO1 activity decreases the synthesis of 5-HT by reducing the amount of Tryptophan availability for 5-HT synthesis by increasing Tryp catabolism via the kynurenine pathway (Plangar et al. (2012) Neuropsychopharmacol Hung 2012; 14(4): 239-244). Increased IDO1 activity and levels of both kynurenine and kynurenic acid have been found in the brains of deceased schizophrenics (Linderholm et al., Schizophrenia Bulletin (2012) 38: 426-432)). Thus, inhibition of IDO1, IDO1, and TDO may also be an important treatment strategy for patients with neurological or neuropsychiatric disease or disorders such as depression and schizophrenia as well as insomnia."

[Nas]

Some interesting quotes from the last link mentioned in my previous post, http://www.nature.com/nbt/journal/v33/n4/fig_tab/nbt0415-321_T1.html :

If anyone believes that there is auto-immunity and inflammation in POIS, then:

" IDO1 and IDO2 are implicated in inflammatory diseases. IDO1 knock-out mice don’t manifest spontaneous disorders of classical inflammation and existing known small molecule inhibitors of IDO do not elicit generalized inflammatory reactions (Prendergast et al. Curr Med Chem. 2011; 18(15):2257-62). Rather, IDO impairment alleviates disease severity in models of skin cancers promoted by chronic inflammation, inflammation-associated arthritis and allergic airway disease. Moreover, IDO2 is a critical mediator of autoantibody production and inflammatory pathogenesis in autoimmune arthritis. IDO2 knock-out mice have reduced joint inflammation compared to wild-type mice due to decreased pathogenic autoantibodies and Ab-secreting cells (Merlo et al. J. Immunol. (2014) vol. 192(5) 2082-2090). Thus, inhibitors of IDO1 and IDO2 are useful in the treatment of arthritis and other inflammatory diseases."


and, another reason to reduce sugars in POIS ( this reminds me of b_jim recent post about taking sugar and noticing increase POIS symptoms after... if kynurenines are indeed one of the causes of POIS cogitive symptoms, then taking sugar increase their toxicity, so it increases POIS symptoms ):

"     Several studies have found Kynurenine pathway metabolites to be neuroactive and neurotoxic. Neurotoxic kynurenine metabolites are known to increase in the spinal cord of rats with experimental allergic encephalomyelitis (Chiarugi et al., Neuroscience, 2001, 102(3):687-95). The neurotoxic effects of Kynurenine metabolities is exacerbated by increased plasma glucose levels. Additionally, changes in the relative or absolute concentrations of the kynurenines have been found in several neurodegenerative disorders, such as Alzheimer’s disease, Huntington’s disease and Parkinson’s disease, stroke and epilepsy (Németh et al., Central Nervous System Agents in Medicinal Chemistry, 2007, 7:45-56; Wu et al. 2013; PLoS One; 8(4)). "

and finally, what I think is also relevant for POIS:

  " Neuropsychiatric diseases and mood disorders such as depression and schizophrenia are also said to have IDO1 and Kynurenine dysregulation. Tryptophan depletion and deficiency of neurotransmitter 5-hydroxytryptamine (5-HT) leads to depression and anxiety. Increased IDO1 activity decreases the synthesis of 5-HT by reducing the amount of Tryptophan availability for 5-HT synthesis by increasing Tryp catabolism via the kynurenine pathway (Plangar et al. (2012) Neuropsychopharmacol Hung 2012; 14(4): 239-244). Increased IDO1 activity and levels of both kynurenine and kynurenic acid have been found in the brains of deceased schizophrenics (Linderholm et al., Schizophrenia Bulletin (2012) 38: 426-432)). Thus, inhibition of IDO1, IDO1, and TDO may also be an important treatment strategy for patients with neurological or neuropsychiatric disease or disorders such as depression and schizophrenia as well as insomnia."

Hi, Quantum I know that this is a silly question but wouldn't peeing after ejaculation help to reduce the immune responce by somewhat cleaning the urinary tract in the penis ?

[Quantum]

Hi, Quantum I know that this is a silly question but wouldn't peeing after ejaculation help to reduce the immune responce by somewhat cleaning the urinary tract in the penis ?

Hi Nas,

Yes, it does make sense, if we suppose that the flow of urine help wash away the remains of semen in the urethra, that would help.  If the "leak" is upper in the ejaculatory ducts, that would't help a lot , though.  But I did include this strategy, last year, in my overall method to control POIS symptoms, but as my pre-pack has become more efficient, I kind of become less disciplined about it.  Mostly because I think it has to occur quite soon after release in order to minimize the immune triggering, and, in my case, most releases happen in a relationship setting, since I am married, so running to the bathroom is not the best way to end an intimate moment with my partner.  But I do think that in a masturbation setting, to urinate, ans also to clean up hands, genitals, and son on, is a good step in a method to minimize POIS symptoms. 

However, my experience is that it is not sufficient in itself to avoid POIS symptoms in a significant manner, and I had to add my pre-pack, which for me is clearly effective, even if I do not urinate after release.

If you dare to share, Nas, let me know of the results you get with this method.

[Nas]

Hi, Quantum I know that this is a silly question but wouldn't peeing after ejaculation help to reduce the immune responce by somewhat cleaning the urinary tract in the penis ?

Hi Nas,

Yes, it does make sense, if we suppose that the flow of urine help wash away the remains of semen in the urethra, that would help.  If the "leak" is upper in the ejaculatory ducts, that would't help a lot , though.  But I did include this strategy, last year, in my overall method to control POIS symptoms, but as my pre-pack has become more efficient, I kind of become less disciplined about it.  Mostly because I think it has to occur quite soon after release in order to minimize the immune triggering, and, in my case, most releases happen in a relationship setting, since I am married, so running to the bathroom is not the best way to end an intimate moment with my partner.  But I do think that in a masturbation setting, to urinate, ans also to clean up hands, genitals, and son on, is a good step in a method to minimize POIS symptoms. 

However, my experience is that it is not sufficient in itself to avoid POIS symptoms in a significant manner, and I had to add my pre-pack, which for me is clearly effective, even if I do not urinate after release.

If you dare to share, Nas, let me know of the results you get with this method.

I do dare to share quantum and yes it did kinda minimize the symptoms by 20 to 40 % which gives further evidance that POIS is an immune response to sperms which makes me think that what we should be working on is to prevent this immune response somehow.

[Quantum]

Hi, Quantum I know that this is a silly question but wouldn't peeing after ejaculation help to reduce the immune responce by somewhat cleaning the urinary tract in the penis ?

Hi Nas,

Yes, it does make sense, if we suppose that the flow of urine help wash away the remains of semen in the urethra, that would help.  If the "leak" is upper in the ejaculatory ducts, that would't help a lot , though.  But I did include this strategy, last year, in my overall method to control POIS symptoms, but as my pre-pack has become more efficient, I kind of become less disciplined about it.  Mostly because I think it has to occur quite soon after release in order to minimize the immune triggering, and, in my case, most releases happen in a relationship setting, since I am married, so running to the bathroom is not the best way to end an intimate moment with my partner.  But I do think that in a masturbation setting, to urinate, ans also to clean up hands, genitals, and son on, is a good step in a method to minimize POIS symptoms. 

However, my experience is that it is not sufficient in itself to avoid POIS symptoms in a significant manner, and I had to add my pre-pack, which for me is clearly effective, even if I do not urinate after release.

If you dare to share, Nas, let me know of the results you get with this method.

I do dare to share quantum and yes it did kinda minimize the symptoms by 20 to 40 % which gives further evidance that POIS is an immune response to sperms which makes me think that what we should be working on is to prevent this immune response somehow.

Hi Nas,

It is quite a good result, 20 to 40% less symptoms, that's a significant progression.  From there, I think you will find other elements for your relief method, and raise that % more still.  Great!


( sorry for the "if you dare to share" expression, I am not sure it is what I wanted to say, I think I should have written "if you agree to share"- it sometimes shows a bit that English is not my native language,when using words I rarely use )

[Nas]

Hi, Quantum I know that this is a silly question but wouldn't peeing after ejaculation help to reduce the immune responce by somewhat cleaning the urinary tract in the penis ?

Hi Nas,

Yes, it does make sense, if we suppose that the flow of urine help wash away the remains of semen in the urethra, that would help.  If the "leak" is upper in the ejaculatory ducts, that would't help a lot , though.  But I did include this strategy, last year, in my overall method to control POIS symptoms, but as my pre-pack has become more efficient, I kind of become less disciplined about it.  Mostly because I think it has to occur quite soon after release in order to minimize the immune triggering, and, in my case, most releases happen in a relationship setting, since I am married, so running to the bathroom is not the best way to end an intimate moment with my partner.  But I do think that in a masturbation setting, to urinate, ans also to clean up hands, genitals, and son on, is a good step in a method to minimize POIS symptoms. 

However, my experience is that it is not sufficient in itself to avoid POIS symptoms in a significant manner, and I had to add my pre-pack, which for me is clearly effective, even if I do not urinate after release.

If you dare to share, Nas, let me know of the results you get with this method.

I do dare to share quantum and yes it did kinda minimize the symptoms by 20 to 40 % which gives further evidance that POIS is an immune response to sperms which makes me think that what we should be working on is to prevent this immune response somehow.

Hi Nas,

It is quite a good result, 20 to 40% less symptoms, that's a significant progression.  From there, I think you will find other elements for your relief method, and raise that % more still.  Great!


( sorry for the "if you dare to share" expression, I am not sure it is what I wanted to say, I think I should have written "if you agree to share"- it sometimes shows a bit that English is not my native language,when using words I rarely use )

Don't worry I didn't take it that way  =)) btw I've noticef that my cognitive symptoms are my main issue here as probably the depression came from my fraustration.

[Quantum]

I've noticef that my cognitive symptoms are my main issue here as probably the depression came from my fraustration.

Hi Nas,

Most POIS sufferers has cognitive symptoms.  In fact, the POIS subtype with no cognitive symptoms, like in my case, is not not common ( I seems to have more emotional symptoms than others, though, when not doing anything to prevent and control the effects of POIS).

The secondary depression and anxiety feeling you mention are true for many members - as time go by, POIS episodes can take their toll on our psychological well being, on a constant basis.  But I think it is easy to discern between secondary emotional symptoms, and the primary ones.  The secondary ones will stay even after a long enough period of abstinence so the acute POIS phase is over.   The primary ones are those that will cause a flare up, an intensification of anxiety, depression, lack of motivation, social avoidance, irritability, and so on, in the days following a release.  This higher level of emotional distress will last as long as the acute POIS phase will last, and returns with each release. 

Some members feel great, as better as ever, after a long enough time of abstinence.  They do not carry underlying depression when POIS is over.  At the other end of the spectrum, there are members who would be anxious or depressed even if they never had POIS  ( I, for one, had anxiety problems long before puberty and POIS.  Even if POIS was worsening tremendously this problem, I had to address this anxiety issue on its own, apart from POIS).

However, like I have expressed, I think both cognitive and emotional clusters of symptoms are related, in POIS, being two branches of the same tree, both coming from inflammatory events in some regions of the brain, a kind of acute, temporary, encephalitis.  In my vision of POIS, they are both a secondary consequence of the immune reaction in the body, causing the immune activation of some enzymes, especially IDO and TDO, then turning on the kynurenine pathways.  Both enzymes can contribute to both clusters of symptoms, and I believe it is the specifics of any individual, its own sensitivities at the metabolic level, that manifest in more or less of each type of symptoms, emotional or cognitive. 

[Nas]

I've noticef that my cognitive symptoms are my main issue here as probably the depression came from my fraustration.

Hi Nas,

Most POIS sufferers has cognitive symptoms.  In fact, the POIS subtype with no cognitive symptoms, like in my case, is not not common ( I seems to have more emotional symptoms than others, though, when not doing anything to prevent and control the effects of POIS).

The secondary depression and anxiety feeling you mention are true for many members - as time go by, POIS episodes can take their toll on our psychological well being, on a constant basis.  But I think it is easy to discern between secondary emotional symptoms, and the primary ones.  The secondary ones will stay even after a long enough period of abstinence so the acute POIS phase is over.   The primary ones are those that will cause a flare up, an intensification of anxiety, depression, lack of motivation, social avoidance, irritability, and so on, in the days following a release.  This higher level of emotional distress will last as long as the acute POIS phase will last, and returns with each release. 

Some members feel great, as better as ever, after a long enough time of abstinence.  They do not carry underlying depression when POIS is over.  At the other end of the spectrum, there are members who would be anxious or depressed even if they never had POIS  ( I, for one, had anxiety problems long before puberty and POIS.  Even if POIS was worsening tremendously this problem, I had to address this anxiety issue on its own, apart from POIS).

However, like I have expressed, I think both cognitive and emotional clusters of symptoms are related, in POIS, being two branches of the same tree, both coming from inflammatory events in some regions of the brain, a kind of acute, temporary, encephalitis.  In my vision of POIS, they are both a secondary consequence of the immune reaction in the body, causing the immune activation of some enzymes, especially IDO and TDO, then turning on the kynurenine pathways.  Both enzymes can contribute to both clusters of symptoms, and I believe it is the specifics of any individual, its own sensitivities at the metabolic level, that manifest in more or less of each type of symptoms, emotional or cognitive.

I see. Thing is that TDO and IDO inhabitors aren't easy to find in pharmacies, hell I don't even think that there is any medication that works on these enzymes. I do think that my symtoms are also emtional but not that strong anyways as I feel normal emosiomally after masturbation but where the most anoying aspect of pois starts with me is when I feel that my brain doesn't work any more It's like all the passion and the deep thoughts I have are gone and when I try to talk to people I feel like all my past social skills are no longer working as my brain blanks when ever someone talks to me and I get bard time understanding what they say. Which all of that causes me to not be able to communicate my feelings to people properly. Which makes relationships with other people like living hell...

[Quantum]

Thing is that TDO and IDO inhabitors aren't easy to find in pharmacies

Pharmacies are not the place where you will find more specific products.  Like for quercetin, the TDO inhibitor I use, it is not carried in pharmacies, usually ( not even in mine neither).  You will find this in natural product stores, natural food stores, those specialized shops who carry organic foods, and all sorts of specialized supplements.  For example, place where they carry the Now foods brand, the brand with the orange labels ( I have even found new places like this by using the store finder of their site , at http://www.nowfoods.com/StoreFinder/ ).  The IDO inhibitor Rosmarinic acid, found in rosemary extract capsules, is also found at this kind of place, though I have been using pure organic rosemary essential oil, one or two drops in half a glass of water, because its camphor-like taste is not a problem for me, and it is very effective.  Essential oil are available at this kind of stores as well.

About six months ago, I have found that some natural products websites were the easiest way, if not the only, for me to get some products that are not available anywhere around here  ( I live in a remote, northern part of Quebec, Canada). Some products were available in maybe only one brand here, expensive or associated with other ingredients I didn't want ( like in the case of quercetin).  I have absolutely no financial interest in it, but the site I prefer now is vitacost.com .  The exact quercetin product I use is this one :  http://www.vitacost.com/vitacost-quercetin-bromelain-120-capsules . tThe bromelain in it enhances quercetin absorption, and the quercetin is in the dihydrate form - the most effective form.  I would use http://www.vitacost.com/solaray-rosemary-leaf-extract-275-mg-45-vegetarian-capsules?q=rosmary+extract&ta=rosmary+extract too, but I am used to rosemary essential oil now.  Curcumin/ turmeric, my second favorite IDO inhibitor, is easier to find, you can even find some in the spice section of your grocery.  I use curcumin with black pepper in it ( piperine), because studies have shown that it greatly enhance the active ingredient absorption.

Like I have said, I have chosen not to use prescription drugs, so I do not use allopurinol  ( why would I use a substance that can have nasty and dangerous side effects when I can use another TDO inhibitor that is completely safe, that is, quercetine ? ).

Other products like the great antioxidant asthaxanthine has not "arrived" yet here, but I have been ordering it online without any problem  ( what I order has absolutely no problematic status, like hallucinogenic properties or possible illicit usage - they are plain, health products, so I never had any customs problems with my orders).

[Nas]

Hay Quantum, long time no talk. But I finally had my querecetine and rosmary extract as my tdo and ido inhabitors but they had abseloutly no effect on me, weather it was before or after orgasm. I only experianced the gama agonist properties of the rosmary extract but I wasn't sure maybe it's only the cane alchole in it lol. Lately I have been orgasming no stop, feeling pretty weak against my urges, which costed me alot in my social life. Anyways I think the tdo and ido inhiniting theory is checked off of my list.

[Quantum]

Hay Quantum, long time no talk. But I finally had my querecetine and rosmary extract as my tdo and ido inhabitors but they had abseloutly no effect on me, weather it was before or after orgasm. I only experianced the gama agonist properties of the rosmary extract but I wasn't sure maybe it's only the cane alchole in it lol. Lately I have been orgasming no stop, feeling pretty weak against my urges, which costed me alot in my social life. Anyways I think the tdo and ido inhiniting theory is checked off of my list.

Hi Nas,

When you say that you feel the gaba agonist properties of rosemary, you mean that it calms you?

Too bad these supplements didn't have any obvious effects for you, but let me express the following comments:

-  I have never used quercetine and rosemary alone against my POIS, I do not know if it would be enough to be efficient for me as well.  The pre-pack I use include much more supplements than that ( listed at http://poiscenter.com/forums/index.php?topic=2090.msg16604#msg16604  ). So far, only one member, G-man,  have shared his experience with a pack very similar to mine ( approx 90% identical), and he has successful relief with it.  The reason I use more substances is that IDO and TDO are essentially for the emotional cluster of POIS symptoms, but I think that POIS has many other clusters of symptoms ( a multi-headed monster).

- My method is based on one ejaculation per week on average - I don't know if it is powerful enough to counter the stacking effects of multiple ejaculations in the same week, let alone the same day.

Good luck, Nas, for your next experiments, and keep on building on the strategy that already brings you 20 to 40% relief, that is, urinating after ejaculation.  From there, you may find something else to raise your level of relief.

[Nas]

I'm thinking about trying the dao supllement to break the histamin, thing is it takes three months for stuff to arrive to my country.And yes the gama effect like the one I had with the librium (the librium is obviously way more effective) I also noticed lately that the zinc gives me a slight relife. And btw the peeing thing is really anoying especially when I feel a burning when I pee.
Lately I was wondering what would cause these cluster of symptoms  especially in the brain there must be a trigerer that bascally causes every single neurotransmitter in the brain to fail. maybe histamine ? or what ever causes the alergic reaction in the body, maybe cells in the body are experiancing inflammation that is effecting their effeciancy ? I mean.... what would connect a sore throats and sneezing with cognitive and emotional problems ? they must have a common ground....

[Quantum]

Hi Nas,

Inflammation symptoms in the body can eventually affect the brain because many of the inflammatory mediators and by-products of the local inflammation reactions ( cytokines, other pro-inflammatory mediator, toxic by-products,...) will eventually cross the blood-brain barrier and affect the homeostasis ( optimal, stable state) of the brain.  Even a non-specific symptom of inflammation like fever can affect the brain ( you will know if you ever get a very high fever and become mentaly confused !).

Since there is no fever in POIS ( at least, not in the vast majority of sufferers), then I think it is inflammatory mediators crossing to the brain that causes the cognitive cluster of symptoms and the emotional cluster of symptoms, and there may be two different pathway for those 2 clusters, because, for exemple, some have more cognitive and less emotional symptoms, some have cognitive symptoms and no emotional symptoms, and some, like myself, have emotional symptoms but no cognitive symptoms. 

If you factor in that POIS may be partly immune reaction and partly neurological reaction, you have to tak einto account the vagus nerve, which is a direct pathway ffrom the body to the brain.  SO, for example, inflammation in the guts can directly affect the brain via the vagus nerve, and some process blocking the vagus anti-inflammatory response will allow for more inflammation to develop.

At this stage of our knowledge, no simple answer can be figured out.  Studies are in progress for both aspects, by Dr Waldinger ( immune) and Dr Komisaruk ( neurological), so we may know much more by the end of next year.

[Nas]

So we can say that the brain cells are ordered by the immune system to be on their defence mechanism. But I have been takeing acylecholincetrase inhabitor and it was supposed to block the inflammantoty transmitters but it didn't seem to work.

[FloppyBanana]

So we can say that the brain cells are ordered by the immune system to be on their defence mechanism. But I have been takeing acylecholincetrase inhabitor and it was supposed to block the inflammantoty transmitters but it didn't seem to work.

Which AcH blocker?
FB

[Nas]

So we can say that the brain cells are ordered by the immune system to be on their defence mechanism. But I have been takeing acylecholincetrase inhabitor and it was supposed to block the inflammantoty transmitters but it didn't seem to work.

Which AcH blocker?
FB

Donepezile

[FloppyBanana]

I never used Donepezile. However from my experience of using AcH blockers you need to take them quite a few hours before O and build up. They will not work if you take them after O from my experience.

Donepezile is quite serious medication. It crosses the blood brain barrier.

Mytelase (AcH blocker) I use does not cross the BB barrier and when used well (can be tricky) it (I believe) stops the shut down message getting to the brain. I tried Rivastigmine (which crossed the BB Barrier) but I noticed I was very snappy (aggressive) when taking it and I had racing thoughts. So I stopped taking it. It didn't really combat POIS either.

You can read my Mytelase experience here: http://poiscenter.com/forums/index.php?topic=2149.0
FloppyB

[Nas]

I don't think so cause I remembered taking the medication at night and at morning and I didn't notice a difference, plus the mytelase is not available in my country so I'm stuck with the donepezile.