GOCOVRI could potentially delay the onset or reduce the progression...........

[dadcor]

Sounds interesting: parkinsonsnewstoday.com/201...

[johntPM]

Your link states:

'“These data suggest that further research is warranted to assess whether GOCOVRI could potentially delay the onset or reduce the progression of motor complications,” Hauser said.'

Gocovri is an extended release version of amantadine. Amantadine is thought to be a minor dopamine agonist. Its advantage is that it has a long halflife, about 14 hours (as compared to 1.5 hours for levodopa/carbidopa). Gocovri is being marketed as a treatment for dyskinesia. I suspect that this is mainly due to the longer halflife giving a more stable effect. This reduction in spikeyness means that plasma levels stay below the threshold for levodopa induced dyskinesia (LID).

If I am correct, you could get a similar effect using existing drugs by carefully timing your doses. In particular, increasing the frequency but reducing the size of your doses.

You can model minute by minute variations in the plasma levels of your drugs using:

parkinsonsmeasurement.org/t...

John

[Bazillion in reply to johntPM]

I like this where did you find it.?

[johntPM in reply to Bazillion]

I wrote the program.

John

[Bridielena in reply to johntPM]

Hello johnPM

I’ve been on it 2 weeks. Immediate relief. It’s just wonderful.

From the first pill I have had virtually no Dyskenesia. The Dyskenesia was dreadful.

I take one about 6.00am and another about 6.00pm.

I can’t say my mobility is much improved with most days taking 5/6 Madopar 125. Some days it’s better than that ....why ....not sure but possibly it’s my diet although I pay strict attention to what and when I have Protein. Also have been having weekly injections of Byetta. Coming off that in a week. We shall see then if my mobility is static or worsens.

Oh yes before bed I take two MadoparHB5....sleep is much better as is my mobility on waking and starting the day.

Not having Dyskenesia though makes me a more tolerant person.

HGE Aus

[tjsmith52 in reply to Bridielena]

Hi...is your dyskinesia “peak dose” or biphasic (when the meds are building up or wearing off?) Thanks!

[Bridielena in reply to tjsmith52]

In the middle. Take pill. Mobility for an hour, Dyskenesia in full battle dress for ????hour, stops, and I know it’s pill time in maybe half an hour. I don’t time myself.

[aspergerian in reply to johntPM]

See also:

The noradrenaline transporter as site of action for the anti-Parkinson drug amantadine.

Sommerauer C, et al. Neuropharmacology 2012.

ncbi.nlm.nih.gov/m/pubmed/2...

And.

Neuronal loss is greater in the locus coeruleus than nucleus basalis and substantia nigra in Alzheimer and Parkinson diseases.

Zarow C, et al. Arch Neurol 2003.

ncbi.nlm.nih.gov/m/pubmed/1...

[johntPM]

The testimony of Bridielena is very compelling:

"I’ve been on it 2 weeks. Immediate relief. It’s just wonderful."

Aspergerian does us a service by reminding us that other mechanisms may be at play.

Ahlskog offers this advice regarding dyskinesia [1]:

"Just as too little brain dopamine translates into motor slowness, too much dopamine results in excessive movements, ie, dyskinesias.

Because dyskinesias represent an excessive response to dopamine replenishment, they can be abolished by reducing the individual doses of carbidopa/levodopa. ...

Unfortunately, reduction of levodopa to abolish dyskinesias may result in reemergence of parkinsonism. Some patients have a narrow therapeutic window between necessary and excessive levodopa effects. For such patients, the old drug amantadine works well to attenuate dyskinesias. If levodopa adjustments cannot control dyskinesias without inducing unacceptable parkinsonism, then the addition of 100 mg of amantadine twice daily is worth considering."

Sharma et al. are more specific [2]:

"Management of peak-dose dyskinesia involves adjustment of levodopa to a smaller and/or more frequent dose and/or reduction or discontinuation of dopamine-enhancing medications, such as MAO-B or COMT inhibitors."

References:

[1] "Cheaper, Simpler, and Better: Tips for Treating Seniors With Parkinson Disease"

J. Eric Ahlskog

Mayo Clin Proc, Dec 2011

ncbi.nlm.nih.gov/pmc/articl...

[2] "Amantadine extended-release capsules for levodopa-induced dyskinesia in patients with Parkinson's disease"

Sharma VD, Lyons KE, Pahwa R

Therapeutics and clinical risk management, April 2018

dovepress.com/amantadine-ex...

John