Anticholinergics are a class of medications that inhibit parasympathetic nerve impulses by selectively blocking the binding of the neurotransmitter acetylcholine to its receptor in nerve cells. The nerve fibers of the parasympathetic system are responsible for the involuntary movements of smooth muscles present in the gastrointestinal tract, urinary tract, lungs, etc. Anticholinergics are divided into three categories in accordance with their specific targets in the central and/or peripheral nervous system: antimuscarinic agents, ganglionic blockers, and neuromuscular blockers......Wickpedia
http://en.wikipedia.org/wiki/Anticholinergic
Why are anticholinergics important?

Hi Paula,
From memory of what I have read, acetylcholine is a chemical messenger which must be in balance with dopamine. The reason for this is one tensions muscles and the other relaxes them, for normal movement. I have seen it described as one "pushes and the other pulls".
Dopamine enables movement and acetylcholine inhibits it.
Since we have reduced levels of dopamine, we need to reduce our levels of acetylcholine to maintain the balance.
So we take an anticholinergic, I take trihexyphenidyl. I find it helps quite a bit, I can tell the difference if I forget to take it.
This is as I understand it, but I have no medical qualifications, and if anyone knows better, please correct me.
Best wishes for Xmas & the New Year to all
Ron

Ron said, "one pushes and the other pulls"

sounds like dystonia to me, until i take meds and they become more balanced. when i took aricept, as i have been sayng, i felt extremely weak peripherally...

i asked for notriptyline simply because i remember taking it early on for weakness from the shins down and it worked..not because i understood anything about cholinergic or inhibitors. Nortriptyline is anti-cholinergic, which means it works as an inhibitor and decreases acetylcholine. it took away the weakness in my lower shins and i got better, when i didn't think i could get better.

i had to give up azilect, which at very low dose, kept me more focused, improved cognition

the neuro suggested aricept for that and later would add nortriptyline

i reluctantly said ok

it made the rest of me feel like my lower legs - i used the words paralyzed and dying. aricept was exactly what i didn't need - it was increasing acetylcholine by blocking the inhibitor, which is what Alzheimers patients need. They lack acetylcholine.

the reason i am talking about this, is i am reading that they are looking away from dopamine to non-dopaminergic therapies, and say we could have cholinergic losses. I am wondering if they mean the inhibitor - and if that means we are running on too much acetylcholine much of the time.

Acetylcholine is used for making pesticides and weaponry. How much of a role is this playing in pd?

paula

I take an anti-cholinergic for bladder function. Comes as a three day patch. One of it's side effects is that makes me more mobile. Noticeably. The urologist knew that it would have this effect, even though it nominally is designed to specifically target acetylcholine receptors in the bladder. There are a couple of other side-effects that are less welcome. One is increased apathy, and the other is falling asleep unexpectedly. If I forget to change the patch I lose both good and bad side effects

Other anticholinergics I have taken for the same problem have had similar effects, though this one takes the prize for both apathy and increased mobility. I am on my 4th drug of this type and my experience is that after some time they lose efficacy and I am back to square one with everything.... the oral ones had many more side-effects and I was happy to get off them......

my posts are being raised from this article, which is an editorial.
AChe is Acetylcholinesterase - the enzyme regulator or inhibitor.

Nicolaas I. Bohnen,
MD, PhD
Roger L. Albin, MD

Neurology

® 2009;73:256–257

note this observation from the authors:

The authors describe prominent and widespread reductions in cortical AChE in the subject groups with dementia and significant reduction of cortical AChE activity in early drug naïvepatients with PD. These findings agree with postmortem evidence suggesting that basal forebrain cholinergic system degeneration appears early in PD and worsens with the appearance of dementia.

my question:

isn't that what one would expect if one were considering acetylcholine in the diagnosis? they have parkinson symptoms by the time they are diagnosed, which would mean their acetylcholine could be high and anticholinergic activity disabled and not working.

then we go on meds, and struggle to keep it balanced, but in advanced patients the meds are less effective so the acetycholine levels go back up as anti cholinergic acitivity decreases once again.

??
paula

E-Move recently sent out an abstract on a study that found "Loss of cholinergic function predicts falling in Parkinson’s disease, according to a new study, independent of dopaminergic denervation."
They reported that
"Thalamic acetylcholinesterase activity derives mainly from terminals of brainstem pedunculopontine nucleus neurons that play a role in the generation of movement,” the authors state, “and loss of AChE is likely to reflect PPN neuron dysfunction or degeneration. Our results are consistent with a key role for the PPN in the maintenance of balance in humans and with PPN dysfunction/degeneration as a cause of impaired postural control and gait in PD.” They suggest that cholinergic therapy may have a role to play in treatment of gait disorder in PD, but “it is uncertain whether the current generation of cholinesterase inhibitors have sufficient brain penetrance to produce meaningful clinical benefits.” (www.mdvu.org)
The journal article : History of falls in Parkinson disease is associated with reduced cholinergic activity

NI Bohnen, MLTM Muller, RA Koeppe, SA studenski, MA Kilbourn, KA Frey, RL Albin

Neurology 2009;73:1670-1676

This seems to fit with the warning that DBS which targets the dopamine pathways should not be expected to improve gait or falling problems.
Anticholinergic drugs (like artane) are not often prescribed currently becuase of their side effects. But maybe this should be a new area of research and drug development? Or is it already?
Note the last sentence in the excerpt above....

'which would mean their acetylcholine could be high and anticholinergic activity disabled and not working.'

Paula,
My understanding is that acetylcholine levels do not go higher, instead an imbalance occurs between acetycholine and dopamine, in other words it is high relative to dopamine. On the other hand thinking about the way that the body works all the time to maintain the right balance of chemicals of all kinds it seems logical that dopamine replacement therapies would stress any balancing mechanisms due to both fluctuating levels in blood and brain, and the breakdown of excess ldopa. This could account for both the low levels in early PD (where the body is trying to keep itself balanced) and the imbalance in late stages (where the whole system is unable to 'understand' how to balance itself due to disregulation from both lack of natural dopamine and replacement drugs).

Ron's statement about one pushes and one pulls is right, and from past reading I believe it it this imbalance that causes tremor - hence increased tremor for some patients who take anti-cholinergic drugs that give benefits for other symptoms, especially if they have not fine-tuned the medication they are taking. And you are, I think, right about it sounding like dystonia too. another manifestation of imbalance between the two.

If this IS a significant piece of research, then there are more than a few issues that arise from it, especially if it can be determined that 'basal forebrain cholinergic system degeneration appears early in PD '. It actually changes the picture of PD and the SN........., weren't early treatments often this class of drug? If so then did doctors then have an understanding of PD that is now not fashionable, but could still be relevant?

My guess is that anti-cholinergic treatments, and their effects probably need to be monitored with as much care as ldopa, so that fragile balancing acts within the brain are not further impaired. And right from the start, by involving the patient early on in being vigilant about their treatment, and encouraging people to observe body response to medication and working with their doctors.

I know the science is your thing, the end result of that science is mine!! So apologies for coming in from a different angle.......
Thanks for opening up a different line of thinking,

Lindy

Great explication, Lindy. I can't add anything to that, but I did find this literature review and history on the use of anticholinergics in treating PD. it's my understanding that the use of this class of drug predates the discovery of levodopa- benadryl was often used. The article mainly discusses the history of Amantadine and covers use in early and late stage PD. I am confused; however, because rather than play a part in causing tremor, I thought that Amantadine actually helped many whose tremor did not respond to l-dopa.

Book: Parkinson's Disease: Diagnosis and Clinical Management
Chapter 33: Amantadine and Anticholinergics by Charles Adler

I must say in defense of our neurologists, how difficult it must be to fine tune PD treatment for each of us, as we all experience it diferently depending on where we are impacted the most (gait vs. tremor vs. bradykinesia). It also highlights how little is still known about what afflicts us.

Laura

thanks, LInda, Lindy and Laura,

I am by no means in a place where i understand this. I'm trying to learn what it means as it sounds like significant changes are being made in research thinking, the nature of which, as it happened just by chance, i directly experienced upon taking aricept.

Had another thought. THey deliberately increase acetylcholine by inhibiting the inhibitor for alzheimers. So does that mean our own inhibitors, when not functioning or gone as they suggest, increase our acetylcholine? I can't quite grasp an understanding yet.

They are also working on a DBS for the PPN. I think Linda's remark about our current anticholinergics being adequate is a good question. I don't understand why we aren't all on an anticholinergic, although side effects occur and is it worth the risk?

paula

My guess is that an anticholinergic on its own would decrease tremor by bringing acetycholine into balance with dopamine levels, but with levodopa is more difficult to balance. Why we are not all on one - there are lots of potential side-effects, especially cognitive and mental, maybe doctors are wary of prescribing them, or even not encouraged to as they are older drugs.....