scenario #2

the dopamine starts decreasing first. this automatically makes acetylcholine the villain and doer of the damage. Truths can come out in good faith....my neck is waaaayyyyy out.

is there a reason that i have obviously not thought of that is going to spring up before me and the johny come lately smack into it like a squeaky clean glass sliding door that you mistook for being open lets you in a mild shock or perhaps even stunned? i'm talking to you....you being anyone else have questions?

I hope members of the crli will join us ......they are a great group of people, if any of you are lurking. we welcome you to join us. You'll find so many needs that you could speak an hour a week to local groups and get invited back. we can still travel, have more covered.. i met so many of you and it felt good. The bond and possibilities are increased a thousand fold if we team up.

the book is titled: the neurotalk guide to the perapitetic pursuit of parkinson's and it is looking goood.

So please clri graduates, you will instantly feel the warmth here and will add so much more to it. From there you can take it to crli and work on presenting the issues discussed here locally regionally or could blog it. All just brainstorming. You will immediately get your own ideas and niche.
There is soooo much we could do. Come on in i say..lol

i'll go back to serious in the next post...but not saying i am not serious here....please join, just jump in.

paula

http://seniors-health-medicare.suite...yne_risks_seen

http://www.naturescountrystore.com/p...ndpanicattacks

http://faculty.washington.edu/chudler/chnt1.html

K Ray Chaudhuri, Anthony HV Schapira
Lancet Neurol 2009; 8: 464–74

Non-dopaminergic treatments in development for
Parkinson’s disease
Susan H Fox, Jonathan M Brotchie, Anthony E Lang

Non-dopaminergic treatments are increasingly being recognised as part of the therapeutic armamentarium fo
Lancet Neurol 2008; 7: 927–38

http://www.thelancet.com/journals/la...068-7/abstract

http://www.chemistryexplained.com/A-...ylcholine.html


http://parkinsons.hopedigest.com/art...mical_ensemble

to be explored with hope: [haven't read yet]
http://scholar.google.com/scholar?hl...-8&oi=scholarr

Lost several so time to quit. When this actually happens to you, as we all know, only those directly affected know ....and i can only hope there are recognized differences and they are working on anticholinergic therapies.

In the meantime, is there something i'm missing?

thank you,
paula

Fingers gave out last night.

Alzheimers patients are given anticholinesterase drugs to allow more acetylcholine. Aricept and exelon are two examples. They inhibit the inhibitor.

Parkinson patients are given the opposite - anticholinergic drugs to keep acetylcholine down. Their acetylcholine levels are normal. Artane and cogentin are two examples. They do the same job as our inhibitor.

These are powerful drugs, but too much acetylcholine is dangerous and even deadly. It slows respiration and slows the pumping of the heart. It interferes with nutrition and paralyzes.

Pesticide poisoning binds to the enzyme that breaks down the acetylcholine [esterase - our natural inhibitor]. pesticide poisoning is up at the top of the suspect list for causing parkinson's.

Pesticide poisoning is not age related.

questions:

Is it eventually dangerous for a pwp to not be on an anticholinergic? i was told several months ago that my heart has a "little backwash that needed to be watched." What is that? A slowing down of my heart?

I was prescribed Aricept and lasted 3 days on it- couldn't breath, felt paralyzed, felt like i was having a heart attack and had overall body weakness - it was extreme. i don't need more acetylcholine.

Overall heath is improved with nortriptyline, altho it is prescribed for other things, it seems to have solved several health problems and took away my peripheral weakness. Can I possibly attribute the last few years of panic, peripheral weakness, and weight loss to too much acetylcholine and not taking an anticholinergic?

WHY ARE THESE ALZHEIMERS DRUGS GIVEN TO AND FDA APPROVED FOR PARKINSON'S?

paula

Paula,

I am sorry for what you have experienced and largely find that doctors, who are really simply reactive to the pharmaceuticals and norms in their field of specialty- they are at essence "yes men and women", generally do not question at a deeper level before scratching something off on the script pad. I'm not saying that doctors can possibly anticipate every possible contraindication for each drug they prescribe; however, a good doctor will take the time to review your chart, think about the implication of prescribing a particular drug for you as an individual with unique needs- as a PWP, your doctor should be particularly concerned with how any neurotropic drug affects the delicate interplay of neurotransmitters. It's bad enough that ours are all a hodge-podge in the first place, and we certainly don't need a doctor giving us a supposed therapy making it worse.

These drugs are what I find the most frightening aspect of living with PD! We already have a highly compromised chemical soup in our brains and then doctors come along and casually prescribe something that might do more harm than good. That being said, I'm sure you saw the thread here on the study showing that anticholinergics mayactually accelerate mental decline. You absolutely did not want to take a cholinergic in conjunction with an anti-cholinergic! See this article at Pharmacy Times

Finally, I'm wondering how much of your negative physical symptoms may be a manifestation of PD's effects on our norepinephrine neurotransmitters? They are profoundly impacted and die off just like dopamine. Why don't we hear or read more about it? Epinephrine controls our sympathetic nervous system and influences heart rate, digestion, swallowing; it's home is in the fight or flight area of our brain, so it is directly linked to physical symptoms of stress or sense of danger. I think there is a lot we can learn from this neglected area of research and plan on posting a new thread on it, but for now I have just discovered that norepinephrine is a major player in PD and it definitely affects us in ways I don't think that researchers have yet fully discovered. This may then, in light of throwing your acetylcholine off balance, along with epinephrine and dopamine (the two work in concert) may have really set things off in your system.

"Parkinson's Disease is more than a Brain Disorder." D. Goldstein. 2000 NINDS Researcher

Laura

Thank you Paula for all your research into acetylcholine. Have to admit whe I first started reading this thread and talking to you about it, I found it hard to understand. But after reading some more, I thik I’m finally getting it. And it jives with the current scientific interest in non-dopaminergic aspects of PD and the need to address these in developing new treatments.

Paula sent me a link to an article that explains the need for correct balance of many neurotransmitters in the brain, especially Acetylcholine. “Anticholergenics are one of the second-line medications that aid some people with Parkinson's. They address an imbalance between acetylcholine and dopamine in the Parkinsonian brain.”
See:
http://parkinsons.hopedigest.com/art...mical_ensemble
Current meds and DBS address only dopamine levels. And current thought is that some PD symptoms, such as gait and balance are not caused by lack of dopamine
Recently EMOVE reported on a study on " Falls in PD Correlate with Cholinergic, not Dopaminergic, Dysfunction” (Neurology 73 November 17, 2009)
that foound..
"… unlike nigrostriatal dopaminergic denervation, thalamic cholinergic denervation is associated with falls in PD... Thalamic AChE activity derives mainly from terminals of brainstem PPN neurons that play a central role in the generation of movement....
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....
Our findings and prior work raise the question as to whether cholinergic therapy may have a place in
the management of mobility problems in PD. Currently approved cholinesterase inhibitors have been
mainly evaluated for cognitive or behavioral benefits in patients with dementia. It is uncertain whether the
current generations of cholinesterase inhibitors have sufficient brain penetrance to produce meaningful
clinical benefits."

note the last sentence. Does anyone know of current research on acetylcholine and PD?

Laura,

You are right about norepinephrine. Here's the nortriptyline page and an excerpt from it:

http://www.medicinenet.com/nortriptyline/article.htm

Like all TCAs, [trycyclic antidepressants] nortriptyline increases levels of norepinephrine and serotonin, two neurotransmitters, and blocks the action of acetylcholine, another neurotransmitter. It is believed that by restoring the balance of these different neurotransmitters in the brain depression is alleviated (for example, the mood is elevated). Nortriptyline was approved by the FDA in November 1964.

I needed an antidepressant, can see that now because of how much better I feel, so yea for norepinephrine too - but that wasn't why i asked for nortriptyline. It also takes away the peripheral problems that left me so weak.
And if i followed the plan, which was to start aricept first, then add nortriptyline, i would have been taking the combination you are talking about. opposing meds - the doctors don't know. i'm wondering who else hasn't really looked hard at this. i'm not suggesting it's going to cure us, but we don't want to be killed either!!

Thanks for the references. i'm going to study norepinephrine too...all of them are important. i have a dystonia post coming.

paula

Linda - a search for "acetylcholine" on MJFF's PD Online Research yields this result:
http://www.pdonlineresearch.org/sear.../acetylcholine

Including this under "Pharmacological Approaches"

"Several small-molecule pharmaceuticals are currently used to treat PD symptoms. Research efforts are aimed at developing new small molecules targeting implicated proteins and processes. Treating dopamine depletion has been a natural focus of therapeutic development, and therapies that increase dopaminergic activity in the brain are among the most efficacious for certain symptoms. These can act either directly on the dopaminergic system or through modulation of synergistic neurotransmitter systems.

Other neurotransmitters involved in PD pathology and symptomatology that are targeted for PD therapeutics development include acetylcholine, glutamate, serotonin, and adenosine."

Cholinesterase inhibitors are what Alzheimers patients need. They block the esterase enzyme inhibitor AChE that most people need. Then more acetycholine builds up. This is what pwp don't need, at least not while younger. Maybe elderly with PD lose acetylcholine but i have a feeling that isn't a given. Are they assuming dementias are all alike or all need acetylcholine?

Here's a definition:
Cholinesterase inhibitors are a group of drugs prescribed to treat symptoms resulting from the early and middle stages of Alzheimer disease.
http://www.answers.com/topic/anticholinesterase-2

from another current study:

NEUROLOGY 2009;73:1670-1676
© 2009 American Academy of Neurology
History of falls in Parkinson disease is associated with reduced cholinergic activity

N. I. Bohnen, MD, PhD, M. L.T.M. Müller, PhD, R. A. Koeppe, PhD, S. A. Studenski, MD, MPH, M. A. Kilbourn, PhD, K. A. Frey, MD, PhD and R. L. Albin, MD

Conclusions: Unlike nigrostriatal dopaminergic denervation, cholinergic hypofunction is associated with fall status in Parkinson disease (PD). Thalamic AChE activity in part represents cholinergic output of the pedunculopontine nucleus (PPN), a key node for gait control. Our results are consistent with other data indicating that PPN degeneration is a major factor leading to impaired postural control and gait dysfunction in PD.

Does that clear it up for anyone? If it does, please explain it to the rest of us.

Abbreviations: AChE = acetylcholinesterase;this is the good guy for pwp and we take anticholinergics to do the same thing. AChE is the bad guy for Alzheimers patients - needs blocked so it can't do it's job ANCOVA = analysis of covariance; MMSE = Mini-Mental State Examination; PD = Parkinson disease; PPN = pedunculopontine nucleus; PSP = progressive supranuclear palsy; UPDRS = Unified Parkinson’s Disease Rating Scale; VOI = volume of interest.

Disclosure: Author disclosures are provided at the end of the article.

Received March 25, 2009. Accepted in final form August 20, 2009.

http://www.neurology.org/cgi/content...act/73/20/1670

The authors and researchers know the difference right? Doctors don't.

Paula - I think that is one of the biggest problems PD patients face - the doctors, even the neuros, aren't keeping up - there is an education gap.

I know we've talked about this before, but have you thought of consulting another doc - preferably a Movement Disorder Specialist? They might at least know what you are talking about!

You could use a medical partner that wants to dig as deep as you do!

Because Ron's statement "one pushes the other pulls" rang my bell, I dug a little here and didn't have to dig hard.

From NINDS:

http://www.ninds.nih.gov/disorders/d..._dystonias.htm

What do scientists know about the dystonias?

Investigators believe that the dystonias result from an abnormality in an area of the brain called the basal ganglia where some of the messages that initiate muscle contractions are processed. Scientists suspect a defect in the body's ability to process a group of chemicals called neurotransmitters that help cells in the brain communicate with each other. Some of these neurotransmitters include:

GABA (gamma-aminobutyric acid), an inhibitory substance that helps the brain maintain muscle control.

Dopamine, an inhibitory chemical that influences the brain's control of movement.

Acetylcholine, an excitatory chemical that helps regulate dopamine in the brain. In the body, acetylcholine released at nerve endings causes muscle contraction.

Norepinephrine and serotonin, inhibitory chemicals that help the brain regulate acetylcholine.

No one treatment has been found universally effective. Instead, physicians use a variety of therapies aimed at reducing or eliminating muscle spasms and pain.

Frequently, the first drug administered belongs to a group that reduces the level of the neurotransmitter acetylcholine. Drugs in this group include trihexyphenidyl, benztropine, and procyclidine HCl. Sometimes these medications can be sedating, especially at higher doses, and this can limit their usefulness.

Again, I have experienced this. I have been waking up with less dystonia - a miracle it seems and one morning i woke up and didn't have any at all. My morning "off" really isn't that bad without dystonia.

It finally dawned on me that I forgot to take nortriptyline until much later than usual the day before. I only take one a day around 3 p.m. hoping it makes for a better evening....my worst time. So last night I did the same thing deliberately and woke up this morning with no dystonia. i got up, cleaned up the kitchen and ate breakfast without having to wait for anything to kick in.

This is truly an improvement for me...I've had dystonia forever it seems.