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ME/CFS: A disease at war with itself
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Cholinergic vs Anticholinergic

Discussion in 'General Treatment' started by xrayspex, Jul 15, 2012.

  1. xrayspex

    xrayspex Senior Member

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    I have a rudimentary understanding of biochemistry and in brain fog right now so tricky to hold all the thoughts in my head that aren't part of my previous educational background

    but I have noticed that cholinergic treatments have been discussed as probably helpful for myelin repair such as ace inhibitors

    http://en.wikipedia.org/wiki/Myelin
    "Demyelination is the loss of the myelin sheath insulating the nerves, and is the hallmark of some neurodegenerative autoimmune diseases,"

    and I think tnf inhibitors may be indicated? I know they are tossed about as good for ME/CFs and autoimmune, right?

    but on the other hand Jay Goldstein recommends for CFS and pain etc combatting histamines because they probably stimulate the NMDA receptors which most experts think we shouldn't do, also correct? NMDA inhibition big idea for CFS I think? So that is why benadryl and other antihistamines often give some relief of symptoms and help with sleep etc
    Yet, benadryl an anticholinergic which is the opposite of what we want to be doing if a myelin problem, as want pro-cholinergic ?

    I am struggling with these competing needs right now as have been using benadryl for sleep and MCS and its the med I can tolerate the best for insomnia yet its anticholinergic effects are worsening my dry eye problem I have with sjogrens. Its very concerning because I have corneal erosion and one eye is constantly blurring and getting recurrent abrasions. yet if I don't take the benadryl at nite I may not sleep and I still work so have to manipulate sleep or will be a mess at the office.

    I don't understand that, how our body/brains seem to like chemicals that are both good and bad for us. what does that mean? (hah sorry if that sounds like forest gump or something, thats the science level I operate at)

    any info appreciated!

    best
    XrS
  2. Bob

    Bob

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    Hi xrayspex, I don't know much about this subject, but I came across this article yesterday, in relation to Alzheimer's disease, and it talks about treatment with choline, uridine and the omega-3 fatty acid DHA in order to encourage brain-cell membrane and synapse growth.

    I don't know if it also relates to myelin sheaths, so I'm just posting it in case it's any help to you.

    MIT News
    Nutrient mixture improves memory in patients with early Alzheimer’s
    In clinical trial, mixture developed at MIT appears to help overcome loss of connections between brain cells.
    July 9, 2012
    http://web.mit.edu/newsoffice/2012/alzheimers-nutrient-mixture-0709.html
  3. Ocean

    Ocean Senior Member

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    Can you try a less drying antihistamine? I use allegra for allergies, although granted it doesn't help with sleep the way Benadryl can. I do very poorly on anticholinergics. The stronger the anticholinergic properties the worse I do.
  4. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    i think that the body has alot of off on switches, i think thats the best way to picture it, especially thinking about neurotransmitters like dopamine, noradrenaline, serotonin, gaba,histamine etc etc Its sort of a guess to which one is stuck on or off. blocking histamine can help us hit the off button, but like u mention it can dry u out, i have the same problems and am constantly using eye drops etc

    Gaba is a definate off switch but sometimes meds that help with this can interrupt our sleep quality or tolerance to meds that effect gaba receptors occurrs. so benzo's need to be used intermittently to keep them effective.

    Things that can help turn the switch off are meds that block the 5ht2 serotonin receptors, this would have less anticholinergic effects. many meds that work on this off switch also effect histamine eg tricyclics, but there are some meds that are more selective and have less cholinergic effects eg mirtazapine/avanza, trazadone.these meds help some with turning the off button off so we can sleep.

    Also alpha receptors eg zanaflex/tizanadine, clonidine, these can also help with the off switch with less cholinergic effects. NMDA receptors u mentioned is how dextromethorphan/robitussin helps some with fibro pain, by blocking the effects of NMDA, this too could possibly help one for sleep.

    Im start to dribble now, too many off on buttons,which one??i dont know lol. just keep hitting them until one turns off,lol. dam sleep, its my achilles.

    cheers!!!
  5. xrayspex

    xrayspex Senior Member

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    thanks heaps, that was a helpful explanation, i was just going to post some new info that relates and you explained the mechanism very understandably

    first, Bob, thx too for the info, I don't do well with fish oil nor eggs (often used for choline supps I think) so have been experimenting to figure out ways to get those things u mentioned to help with dry eye etc This is interesting study that explains a bit more why choline good for us and how it ties into the regulation of gluatamate which seems to be sort of a core issue that all roads in my research seem to be leading to with our problems:


    CDP-choline prevents glutamate-mediated cell death in cerebellar granule neurons.

    Mir C, Clotet J, Aledo R, Durany N, Argemí J, Lozano R, Cervós-Navarro J, Casals N.
    Source

    Unit of Molecular and Cellular Biology, Faculty of Health Sciences, International University of Catalonia, Barcelona, Spain.
    "Cytidine 5'-diphosphocholine (CDP-choline) has been shown to reduce neuronal degeneration induced in central nervous system (CNS) injury. "

    http://www.ncbi.nlm.nih.gov/pubmed/12663935

    So this interesting issue of regulating Glutamate, that is the question.
    Glutamate is associated with improved energy on the positive side but pain and other health problems on the negative side.
    So these things that can turn our buttons off, in Heapsreal words, like benadryl, also worsen our memory. double bind.

    So this explains why when my doc tried me on provigil in 2006 my eyes got messed up and I started to feel really bad, it did help cut back pain but I got anhedonia. It increases glutamate and thus the alertness it helps with yet because a lot of us need sedating meds to decrease overexcitatory stuff going on with nmda etc it provigil can be hurtful, probably why its one of the meds on Dr Cheney's absolutely not list.
    I think my eyes didnt fully recover and it may have worsened the autoimmune issues evolving.

    The vigilance promoting drug modafinil increases extracellular glutamate levels in the medial preoptic area and the posterior hypothalamus of the conscious rat: prevention by local GABAA receptor blockade.

    http://www.ncbi.nlm.nih.gov/pubmed/10088135
    Neuropsychopharmacology. 1999 Apr;20(4):346-56.



    This study explains pretty well the good and bad of glutamate and also posits that glutamate antagonists fight cancer, I dont know if later studies confirm. It also says, I think, that calcium increased can be dangerous and increase risk for cancer?

    Glutamate antagonists: Deadly liaisons with cancer



    http://www.pnas.org/content/98/11/5947.full
    Bob likes this.
  6. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    evening primrose oil if u cant tolerate fishoil??
  7. xrayspex

    xrayspex Senior Member

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    ocean, does allegra help you sleep? never tried it. I tried atarax a couple mo.s ago cus less antichol props but wow, it induced oxygen hunger bad at low dose, felt depleted of oxygen, and also I think it caused a nosebleed, odd. never had nosebleed before. tried it over a week.

    i havent tried clonidine, maybe should, for sleep.have any of you? didnt like trazadone, tricyclics nor benzos.
  8. xrayspex

    xrayspex Senior Member

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    heaps yea I was taking primrose for about a year but I stopped it recently because trying to figure out what was causing these killer headaches and pain attacks that started in last year.

    I may add it back in again later but I forget now, when i researched it more there was something negative about it, maybe its associated with increased headache. maybe it does a little of both: decrease glutamate and increase it.
  9. heapsreal

    heapsreal iherb 10% discount code OPA989,

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  10. xrayspex

    xrayspex Senior Member

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    yea I found it heaps, one downside of primrose is it may make one more vulnerable to seizure

    http://www.nlm.nih.gov/medlineplus/druginfo/natural/1006.html

    and anticonvulsants have been pretty effective for me (gabapentin, topamax, experimenting with lately, really helps with pain and headaches but some weird side fx, really low dose ) so taking stuff that does opposite of that not wise for me, altho still want my black tea.....anyway that does make me wonder if primrose has dual props, seizure induction sounds like glutamate agonist, but if it helps like choline does that sounds like gaba antagonist......dunno
  11. xrayspex

    xrayspex Senior Member

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    thx for the blue lite link heaps will go take a look
    its a research day!
    heapsreal likes this.
  12. heapsreal

    heapsreal iherb 10% discount code OPA989,

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  13. Ocean

    Ocean Senior Member

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    I haven't noticed that it helps in a significant way. For sleep vit D and mag. have helped me.
  14. adreno

    adreno 3% neanderthal

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    Anticholinergics are sedative, and will therefore usually help with sleep, but they also have detrimental effects on cognition and the cardiovascular system. If you want to avoid that, there are both antihistamines and sleep meds which aren't anticholinergic.
  15. Ema

    Ema Senior Member

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    Have you ever looked into DHEA eye drops? I know some people with Sjogren's that have used them and they certainly helped me with my dry eyes before I got my DHEA levels up with the oral supplements.

    They can even be used with normal DHEA levels as the effects are not systemic.

    I wish I knew more about the actual topic of this thread!
  16. xrayspex

    xrayspex Senior Member

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    adreno what are some good antihistamines with no anticholinergic? I have tried many meds and supps over the years and only reason I take benadryl is its one i can tolerate better than others. as I said earlier can't do tricyclics, benzos, ssri, snri, none of natural sleep aids help, feel horrible on claritin, atarax a no go......I take benadryl mostly for sleep but sometimes it helps with chem sensitivity but I dont like to take during day much, just a tinch if I do

    and Ema can one get the dhea over the counter or need script? glad its not systemic because I don't tolerate hormones of any kind over the years.
  17. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    i know its controversial at the moment, not quite benzo's but zopiclone and zolpidem have a short half life so u shouldnt get any hangover from them like traditional benzo's, also not suppose to affect sleep phases as much either. dont know if u have tried them yet??
  18. xrayspex

    xrayspex Senior Member

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    hi heaps! no I haven't heard of them, I will do some more research, thanks :)

    ps I am not against benzos, just don't feel good on them myself, but if I tolerated them better and they helped I certainly would use them.....after years of this, whatever works! I have used teeny bits in the past but let it go because would get bad mood hangover from it


    oh ok, googled, yep, tried ambien and sonata, nope, can't do 'em
    ambien works, but it disorganized my brain really badly next day, not worth it, and sonata i forget why, think it wasnt as effective and the bad mood thing

    I could try a different benzo, it was klonopin mostly I tried
  19. adreno

    adreno 3% neanderthal

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    I agree with heaps on the Z-drugs as far as sleep meds go. WRT antihistamines, I find loratadine very tolerable. Other choices would be cetirizine, ebastine or fexofenadine.
  20. heapsreal

    heapsreal iherb 10% discount code OPA989,

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    i have been reading a heap on dmx/dextromethorphan and how it helps lower benzo tolerance as well as how it works generally. Man its a complicated drug, seems to be used by alot in higher doses to get high on, im not into that but look into its effects on NMDA and reversing benzo tolereance at much lower doses, also seems to help with narcotic tolerance so people can use less and get good pain relief. researching this is giving me a headache, if anyone has any good links for this it would be great.

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