I have been a bit surprised to hear that many with dyskinesias believe it to be caused by the combined use of l-dopa and an agonist. Does anyone here have dyskinesias and is NOT taking an agonist?

It's very interesting that Rick quit Requip and his dyskinesias went away...has anyone else quit an agonist and had dyskinesia go away? I also noted Paula's comment, today I think, that comtan gave her dyskinesias and that when she quit taking it, they went away, or at least that's what I got from the post.

Our neuro is really pushing comtan...I hate to add another drug unless we could quit the mirapex at the same time, that might actually make it worth trying.

i've been adjusting meds since my aricept "experience' which set me on a neurotransmitter journey. So this is a recent med protrocol and it involves quite a few "heavy duty " drugs but except for sinemet, no dopaminergics. I didn't realize this until i got dosages right. Many years ago they were making people on DAs give up their drivers license because of "sleep attack" risk in canada. There may be people there that only take sinemet and i'd love to hear from anyone else who has this blend.

We could make a pwp chemical protocol guide. Recipe Book.

adding that above line was a wise crack and really I'd like to know if we actually need tbem both at the same time. People are taking both to avoid dyskinesia but that in itself may cause it; especially in more advanced patients.

The D-2 Dopamine Receptor

Although there are five distinct types of dopamine receptors, they fall into two broad categories: excitatory and inhibitory. As the labels suggest, the former activates a process while the latter prevents it or regulates it in some way. The D2 receptor falls into the latter category. [inhibitory] When the dopamine process is interrupted, the result can be any one of a wide range of neuro-psychiatric and movement disorders that can include not only tardive dyskinesia, but Tourette's syndrome, Parkinson's disease and others.

http://www.tardivedyskinesia.com/tre...e-agonists.php


Exp Neurol. 2010 Aug;224(2):395-402. Epub 2010 May 7.
Dyskinetic potential of dopamine agonists is associated with different striatonigral/striatopallidal zif-268 expression.

Carta AR, Frau L, Pinna A, Morelli M.
Department of Toxicology, University of Cagliari, Cagliari, Italy; Centre of Excellence for Studies on Neurobiology of Addiction, Cagliari, Italy. acarta@unica.it
Exp Neurol. 2010 Nov;226(1):11-4.
Abstract

In the dopamine-depleted striatum, an altered post-synaptic signalling of efferent neurons might underline the onset of variable dyskinetic responses to dopaminergic agonists. We have previously shown that a subchronic treatment with the D1 agonist SKF-38393 and the D2 agonist ropinirole induces a dyskinetic response of high and low intensities respectively, in 6-hydroxydopamine-lesioned rats. Here, zif-268 mRNA expression was evaluated in striatonigral and striatopallidal neurons to assess a neurochemical marker of these different dyskinetic responses upon drug administration. Acute and subchronic SKF-38393 (3mg/kg) increased zif-268 expression per neuron in the striatonigral pathway, albeit the number of neurons displaying high early-gene levels was reduced by the subchronic treatment. Zif-268 mRNA in striatopallidal neurons was not affected by SKF-38393 treatments. In contrast, ropinirole (5mg/kg) did not alter zif-268 mRNA in striatonigral neurons acutely, whereas ropinirole decreased zif-268 mRNA subchronically. Both acute and subchronic ropinirole decreased zif-268 levels in the striatopallidal pathway. The differential expression of zif-268 in striatonigral and striatopallidal neurons might provide a biochemical correlate of the dyskinetic outcome displayed by SKF-38393 and ropinirole treatments, suggesting that evaluation of neuronal responses upon drug administration provides a tool for the preclinical characterization of dyskinetic potential beyond behavioural tests.


http://www.ncbi.nlm.nih.gov/pubmed/20452347

I am going to turn to the research to highlight how very little is known about Levodopa Induced Dyskinesia (LID). This recent study indicates that genetics and our exposure to tobacco influences our likelihood of developing dyskinesia. People who have never smoked and who have an alteration impacting their D2 receptors are more likely to get dyskinesia and to see it appear earlier.

Just as an aside, most research on dyskinesia seems to center on the dopamine receptors and the timing of synaptic stimulation. Note: Dyskinesia is nearly non-existant in Duodopa patients. Dyskinesia is less to do with levodopa, and much more to do with delivery and maintaining consistent therapeutic plasma levels. When there is too much circulating in us at once, we get the wiggles. BTW, it's funny that the focus is on the extra movement, for me, I feel so wiped out by it, I can take half a day to get back on the 'normal' train.

Since there is a strong correlation between receptors and LID, and agonists work solely with our receptors, it would seem logical that if taken with levodopa, we might get a little more dyskinetic. I once mistakenly took 2 doses of Sinemet while only using that drug. I had a reaction, but it was not dyskinesia.

Further, when neuros try to make the case that levodopa be avoided or delayed, they really have nothing to base it on save a few studies that show you may delay levodopa therapy for a few years. What they don't tell you that is longitudinally, after 5-6 years of diagnosis, patients will have roughly same med needs with Sinemet and experience the same level of dyskinesia and those first years, those patients had to live with inferior symptom control or were undermedicated. I really don't know how someone could even tolerate the side effects of an agonist if you have to go beyond the barely therapeutic dosages. At lower dosages I already had behavior problems. At the levels we would need go to sustain clinical benefit, I could not imagine what might happen. The notion that levodopa therapy should be delayed dates back to 1978! Current recommendation of the AAN is to use what improves quality of life most for patient in balance with long term need for levodopa.

I understand why they want to delay dyskinesia, but now genetics may play a role in that too? Yeesh, at this point, I'd be most impressed with a doctor who promoted daily exercise over all else as the most important treatment early on; it costs nothing, and has the best side effect profile.

Laura

I suffer with "wearing off" dyskinesia and take only sinemet - no agonist, no comptan. The dyskinesia started as soon as I started sinemet. It has increased over time and decreased my "on time". Interesting comments from Laura. I have never smoked and did not start sinemet until 4 years after diagnosis. I am tremor dominant and the sinemet does help just does not last as long as it did when I started it. Increasing dosage or decreasing dosage intervals results in more dyskinesia.

Sunflower

Thanks for sharing your experience. I would get a mild chorea form of dyskinesia when on agonists and levodopa, but levodopa alone and I am fine. We think more goes into the wearing off and dyskinesia stuff, we have a threa from a few months ago. Doesn't it stand to reason that the less you weigh, the more you will have excess levodopa circulating around? I think there are less than 20 references out there, but scientists have noted that our BMI does indeed impact levodopa absorption levels. If you want to add your weight to our info, please just PM the number.

Thanks!

Laura

Greetings,


I've been taking carb/levo generic regular and then ER for three years and 3 months respectively. I've never taken an agonist of any kind until today (requip). I definitely had dyskenesias from regular sinement. At times, it was significant (too wired) and at other times no problem.

Any tips, words of wisdom, on starting my first day on Requip? Taking 2 mg once per day along with 1 reg c/l and 1 ER c/l.

Cheers,

Hi oneguy,

i've been meaning to reply sooner but there are so many good discussions, some on the intense side; this forum is run by malfunctioning hardware . possibly from a virus. it manifests itself in so many ways; I'm hoping you have a sense of humor.

my point earlier in this thread is that a fairly recent med change has led me to conclude about myself and others have thought it too,that l-dopa in anyother form than regular 25/100s, causes dyskinesia, but after having pd for 20 + years i was surprised and pleased to see that i could actually control most of it unless i 'm out later and have to take even more.

i have said several times that i take 2 25/100 every two hours. i don't always remember doses but that is what my body needs now. i take 2 amantadine. i'll ofer up some evidence and if all goes well LLinda H. and Peg may visit this winter - i sure hope it's warmer down here! ..and they will be my qualified witnesses.

Today's witness is my husband after a busy day of Christmas shopping. After taking 10 sinemet beginning' at 6:15. i emphasized emphatically that i had to be accurate in sayihg something like this in a public forum.

Am i dyskinetic? At anytime was I dyskinetic? He said no not at all but you still get your bird beak mouth thing . But you don't have it right now.


ah my point being that even the ER -which i guess is extended release? made me dyskinetic. i would expect , if you are like me, you to be dyskinetic on both requip and regular sinemet and even more so if you add ER or as it is called here-CR. i am only taking a dosage that i can control the best.

let us know? - you don't have to go through all that expermentation with agonists necessarily. it's worth avoiding some true personality changes and reckless behaviors altho the same warning comes with with sinemet now with no fanfare or attention drawn to it. Like they do with congressional bills slip it on in there and don't tell.

i am looking for people who can conclude that theyare not dyskinetic on l dopa? It might be possible that it takes more sinemet to get out of dyskinesia.

And amantadine works.

Paula,

I too have wondered if more sinemet could get past the dyskinesia. I have tried increasing it slowly but the dyskinesia seems to get worse. I have often wondered if there is a threshold I have to reach before the dyskinesia disappears. You posted a whle back that you had alot of dyskinesia. What changes did you make to get to where you are now? I can't take more than 1 amantadine a day or my eyes get very painful and scratchy. My dyskinesia seems to increase throughout the day and the sinemet lasts less time. I take my last sinemt at 5:00. It lasts until 6:30 - 7:00 and then I have dyskinesia for 1/2 to 1 hr followed by extreme tremor but about 9:00 I seem to have little tremor and can function almost normally. Think after Christmas will experiment a bit more and see if an increase can help me. My MDS once commented that he felt if I could past the dose I was on the dyskinesia might diminish. I have always been of the mindset that less is better. Maybe that is not the case for me.

Sunflower

Are you only taking the regular sinemet or CR? i dropped every thing else, including comtan, CR, stalevo. I take two amantadine but i also added nortriptyline...brand name pamelor. It boosts norepinephrine uptake [we are also lacking these cells annd they don't include it often in defining parkinson's]. Some think the disappearance of norepinephrine transmitter cells is extremely important with pd so i hope someone is paying attention to the transmitters , whch seem to me. on the surface appear to have the potential for defining pd and the biomarkers that say it all. If we deplete our transmitters there will be inflammation, all kinds of motor abnormalities and mental illness. It has to become at some point auto immune.

anyway some consider norapinephrine to be neuroprotective but i think it also helps dyskinesia;does lack of norapinephrine contribute to a cascade of dysfunction by gradually disappearing like dopamine? pamelor has anticholinergic properties and i would suggest you ask you doctor about anticholinergics and Pamelor especially. It lowers actetylcholine, a neurotransmitter that is responsible for smooth muscle movements and it gets too out of balance. It also makes sense to take an antidepressant that boosts norapinephrine.

this all happens in our gut too, which is a whole other area of this illness. so how can they figure all this out with little cameras that go everywhere in our bodies

they can give you brain fog tho.

did you say you had a DBS? i can't recall.

here's my list:

2 25/100 regular generic levodopa carbidopa every two hours - usually between 1400 to 1600 mgs to get thru a night out.

2 amantadine

4 10 mg of pamelor - this is a low dose
2 or 3 xanax for anxiety and sleep -very low dose .05mg
nexium
synthroid - hypothyroid

my question is why do we get end of dose dyskinesia? that kind of ties in with this and makes me wonder if i could have tardive dyskinesia. there's so much to check up on. one of my warning signs for going off is head bobbing. why dyskinesia when off?

i appreciate your input and please let me know what you discover.

so the only dopaminergic drug i take is regular sinemet.